---
_id: '12119'
abstract:
- lang: eng
text: Intravascular neutrophils and platelets collaborate in maintaining host integrity,
but their interaction can also trigger thrombotic complications. We report here
that cooperation between neutrophil and platelet lineages extends to the earliest
stages of platelet formation by megakaryocytes in the bone marrow. Using intravital
microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions,
termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent
migration towards perisinusoidal megakaryocytes, plucking neutrophils actively
pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated
kinase activation through reactive oxygen species. By these mechanisms, neutrophils
accelerate proplatelet growth and facilitate continuous release of platelets in
steady state. Following myocardial infarction, plucking neutrophils drove excessive
release of young, reticulated platelets and boosted the risk of recurrent ischemia.
Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent
thrombosis after myocardial infarction and thrombus burden in venous thrombosis.
We establish neutrophil plucking as a target to reduce thromboischemic events.
acknowledgement: "We thank Coung Kieu and Dominik van den Heuvel for excellent technical
assistance. This work was supported by the German Research Foundation (PE2704/2-1,
PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR
332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12
to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework
of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German
Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833).
This project has received funding from the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program (grant agreement
No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon
2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement
no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e
Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network
of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by
the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence
(CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical
Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G.
was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’
by the German Federal\r\nMinistry of Education and Research to the German Center
for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care
through the research project DigiMed Bayern."
article_processing_charge: No
article_type: original
author:
- first_name: Tobias
full_name: Petzold, Tobias
last_name: Petzold
- first_name: Zhe
full_name: Zhang, Zhe
last_name: Zhang
- first_name: Iván
full_name: Ballesteros, Iván
last_name: Ballesteros
- first_name: Inas
full_name: Saleh, Inas
last_name: Saleh
- first_name: Amin
full_name: Polzin, Amin
last_name: Polzin
- first_name: Manuela
full_name: Thienel, Manuela
last_name: Thienel
- first_name: Lulu
full_name: Liu, Lulu
last_name: Liu
- first_name: Qurrat
full_name: Ul Ain, Qurrat
last_name: Ul Ain
- first_name: Vincent
full_name: Ehreiser, Vincent
last_name: Ehreiser
- first_name: Christian
full_name: Weber, Christian
last_name: Weber
- first_name: Badr
full_name: Kilani, Badr
last_name: Kilani
- first_name: Pontus
full_name: Mertsch, Pontus
last_name: Mertsch
- first_name: Jeremias
full_name: Götschke, Jeremias
last_name: Götschke
- first_name: Sophie
full_name: Cremer, Sophie
last_name: Cremer
- first_name: Wenwen
full_name: Fu, Wenwen
last_name: Fu
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Hellen
full_name: Ishikawa-Ankerhold, Hellen
last_name: Ishikawa-Ankerhold
- first_name: Elisabeth
full_name: Raatz, Elisabeth
last_name: Raatz
- first_name: Shaza
full_name: El-Nemr, Shaza
last_name: El-Nemr
- first_name: Agnes
full_name: Görlach, Agnes
last_name: Görlach
- first_name: Esther
full_name: Marhuenda, Esther
last_name: Marhuenda
- first_name: Konstantin
full_name: Stark, Konstantin
last_name: Stark
- first_name: Joachim
full_name: Pircher, Joachim
last_name: Pircher
- first_name: David
full_name: Stegner, David
last_name: Stegner
- first_name: Christian
full_name: Gieger, Christian
last_name: Gieger
- first_name: Marc
full_name: Schmidt-Supprian, Marc
last_name: Schmidt-Supprian
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Isaac
full_name: Almendros, Isaac
last_name: Almendros
- first_name: Malte
full_name: Kelm, Malte
last_name: Kelm
- first_name: Christian
full_name: Schulz, Christian
last_name: Schulz
- first_name: Andrés
full_name: Hidalgo, Andrés
last_name: Hidalgo
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
citation:
ama: Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes
drives platelet production and boosts cardiovascular disease. Immunity.
2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001
apa: Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M.,
… Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet
production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001
chicago: Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin,
Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives
Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier,
2022. https://doi.org/10.1016/j.immuni.2022.10.001.
ieee: T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives
platelet production and boosts cardiovascular disease,” Immunity, vol.
55, no. 12. Elsevier, p. 2285–2299.e7, 2022.
ista: Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul
Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz
M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K,
Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm
M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes
drives platelet production and boosts cardiovascular disease. Immunity. 55(12),
2285–2299.e7.
mla: Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet
Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12,
Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001.
short: T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L.
Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S.
Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach,
E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian,
F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity
55 (2022) 2285–2299.e7.
date_created: 2023-01-12T11:56:54Z
date_published: 2022-12-13T00:00:00Z
date_updated: 2023-08-03T14:21:51Z
day: '13'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2022.10.001
ec_funded: 1
external_id:
isi:
- '000922019600003'
pmid:
- '36272416'
file:
- access_level: open_access
checksum: 073267a9c0ad9f85a650053bc7b23777
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T10:18:48Z
date_updated: 2023-01-23T10:18:48Z
file_id: '12341'
file_name: 2022_Immunity_Petzold.pdf
file_size: 5299475
relation: main_file
success: 1
file_date_updated: 2023-01-23T10:18:48Z
has_accepted_license: '1'
intvolume: ' 55'
isi: 1
issue: '12'
keyword:
- Infectious Diseases
- Immunology
- Immunology and Allergy
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 2285-2299.e7
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Immunity
publication_identifier:
issn:
- 1074-7613
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neutrophil “plucking” on megakaryocytes drives platelet production and boosts
cardiovascular disease
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 55
year: '2022'
...
---
_id: '12133'
abstract:
- lang: eng
text: Social distancing is an effective way to prevent the spread of disease in
societies, whereas infection elimination is a key element of organismal immunity.
Here, we discuss how the study of social insects such as ants — which form a superorganism
of unconditionally cooperative individuals and thus represent a level of organization
that is intermediate between a classical society of individuals and an organism
of cells — can help to determine common principles of disease defence across levels
of organization.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Sylvia
full_name: Cremer, Sylvia
id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87
last_name: Cremer
orcid: 0000-0002-2193-3868
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Cremer S, Sixt MK. Principles of disease defence in organisms, superorganisms
and societies. Nature Reviews Immunology. 2022;22(12):713-714. doi:10.1038/s41577-022-00797-y
apa: Cremer, S., & Sixt, M. K. (2022). Principles of disease defence in organisms,
superorganisms and societies. Nature Reviews Immunology. Springer Nature.
https://doi.org/10.1038/s41577-022-00797-y
chicago: Cremer, Sylvia, and Michael K Sixt. “Principles of Disease Defence in Organisms,
Superorganisms and Societies.” Nature Reviews Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41577-022-00797-y.
ieee: S. Cremer and M. K. Sixt, “Principles of disease defence in organisms, superorganisms
and societies,” Nature Reviews Immunology, vol. 22, no. 12. Springer Nature,
pp. 713–714, 2022.
ista: Cremer S, Sixt MK. 2022. Principles of disease defence in organisms, superorganisms
and societies. Nature Reviews Immunology. 22(12), 713–714.
mla: Cremer, Sylvia, and Michael K. Sixt. “Principles of Disease Defence in Organisms,
Superorganisms and Societies.” Nature Reviews Immunology, vol. 22, no.
12, Springer Nature, 2022, pp. 713–14, doi:10.1038/s41577-022-00797-y.
short: S. Cremer, M.K. Sixt, Nature Reviews Immunology 22 (2022) 713–714.
date_created: 2023-01-12T12:03:14Z
date_published: 2022-12-01T00:00:00Z
date_updated: 2023-08-04T08:53:32Z
day: '01'
department:
- _id: SyCr
- _id: MiSi
doi: 10.1038/s41577-022-00797-y
external_id:
isi:
- '000871836300001'
pmid:
- '36284178'
intvolume: ' 22'
isi: 1
issue: '12'
keyword:
- Energy Engineering and Power Technology
- Fuel Technology
language:
- iso: eng
month: '12'
oa_version: None
page: 713-714
pmid: 1
publication: Nature Reviews Immunology
publication_identifier:
eissn:
- 1474-1741
issn:
- 1474-1733
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Principles of disease defence in organisms, superorganisms and societies
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 22
year: '2022'
...
---
_id: '12272'
abstract:
- lang: eng
text: Reading, interpreting and crawling along gradients of chemotactic cues is
one of the most complex questions in cell biology. In this issue, Georgantzoglou
et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo
models to map the temporal sequence of how neutrophils respond to an acutely arising
gradient of chemoattractant.
article_number: e202206127
article_processing_charge: No
article_type: original
author:
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: 'Stopp JA, Sixt MK. Plan your trip before you leave: The neutrophils’ search-and-run
journey. Journal of Cell Biology. 2022;221(8). doi:10.1083/jcb.202206127'
apa: 'Stopp, J. A., & Sixt, M. K. (2022). Plan your trip before you leave: The
neutrophils’ search-and-run journey. Journal of Cell Biology. Rockefeller
University Press. https://doi.org/10.1083/jcb.202206127'
chicago: 'Stopp, Julian A, and Michael K Sixt. “Plan Your Trip before You Leave:
The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology. Rockefeller
University Press, 2022. https://doi.org/10.1083/jcb.202206127.'
ieee: 'J. A. Stopp and M. K. Sixt, “Plan your trip before you leave: The neutrophils’
search-and-run journey,” Journal of Cell Biology, vol. 221, no. 8. Rockefeller
University Press, 2022.'
ista: 'Stopp JA, Sixt MK. 2022. Plan your trip before you leave: The neutrophils’
search-and-run journey. Journal of Cell Biology. 221(8), e202206127.'
mla: 'Stopp, Julian A., and Michael K. Sixt. “Plan Your Trip before You Leave: The
Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology, vol. 221,
no. 8, e202206127, Rockefeller University Press, 2022, doi:10.1083/jcb.202206127.'
short: J.A. Stopp, M.K. Sixt, Journal of Cell Biology 221 (2022).
date_created: 2023-01-16T10:01:08Z
date_published: 2022-07-20T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '20'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1083/jcb.202206127
external_id:
isi:
- '000874717200001'
pmid:
- '35856919'
file:
- access_level: open_access
checksum: 6b1620743669679b48b9389bb40f5a11
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T10:39:34Z
date_updated: 2023-01-30T10:39:34Z
file_id: '12451'
file_name: 2022_JourCellBiology_Stopp.pdf
file_size: 969969
relation: main_file
success: 1
file_date_updated: 2023-01-30T10:39:34Z
has_accepted_license: '1'
intvolume: ' 221'
isi: 1
issue: '8'
keyword:
- Cell Biology
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
issn:
- 0021-9525
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
related_material:
record:
- id: '14697'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 'Plan your trip before you leave: The neutrophils’ search-and-run journey'
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 221
year: '2022'
...
---
_id: '10703'
abstract:
- lang: eng
text: 'When crawling through the body, leukocytes often traverse tissues that are
densely packed with extracellular matrix and other cells, and this raises the
question: How do leukocytes overcome compressive mechanical loads? Here, we show
that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness
requires neither force sensing via the nucleus nor adhesive interactions with
a substrate. Upon global compression of the cell body as well as local indentation
of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into
dot-like structures, providing activation platforms for Arp2/3 nucleated actin
patches. These patches locally push against the external load, which can be obstructing
collagen fibers or other cells, and thereby create space to facilitate forward
locomotion. We show in vitro and in vivo that this WASp function is rate limiting
for ameboid leukocyte migration in dense but not in loose environments and is
required for trafficking through diverse tissues such as skin and lymph nodes.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner
for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes
Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll
for advice on fluorescent labeling of collagen gels. This research was supported
by the Scientific Service Units (SSUs) of IST Austria through resources provided
by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron
Microscopy Facility. This work was funded by grants from the European Research Council
( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding
from the European Union’s Horizon 2020 research and innovation program under the
Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Gaertner, Florian
last_name: Gaertner
- first_name: Patricia
full_name: Reis-Rodrigues, Patricia
last_name: Reis-Rodrigues
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Juan
full_name: Aguilera, Juan
last_name: Aguilera
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive
actin patches to facilitate immune cell migration in dense tissues. Developmental
Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024
apa: Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl,
M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate
immune cell migration in dense tissues. Developmental Cell. Cell Press ;
Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024
chicago: Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons,
Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive
Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental
Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024.
ieee: F. Gaertner et al., “WASp triggers mechanosensitive actin patches to
facilitate immune cell migration in dense tissues,” Developmental Cell,
vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.
ista: Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner
AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK.
2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues. Developmental Cell. 57(1), 47–62.e9.
mla: Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to
Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell,
vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.
short: F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl,
A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild,
M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.
date_created: 2022-01-30T23:01:33Z
date_published: 2022-01-10T00:00:00Z
date_updated: 2024-03-27T23:30:23Z
day: '10'
ddc:
- '570'
department:
- _id: MiSi
- _id: EM-Fac
- _id: NanoFab
- _id: BjHo
doi: 10.1016/j.devcel.2021.11.024
ec_funded: 1
external_id:
isi:
- '000768933800005'
pmid:
- '34919802'
intvolume: ' 57'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.sciencedirect.com/science/article/pii/S1534580721009497
month: '01'
oa: 1
oa_version: Published Version
page: 47-62.e9
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: Developmental Cell
publication_identifier:
eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Cell Press ; Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 57
year: '2022'
...
---
_id: '12401'
abstract:
- lang: eng
text: "Detachment of the cancer cells from the bulk of the tumor is the first step
of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear,
which factors contribute to this step.\r\nRecent studies indicate a crucial role
of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying
cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological
microenvironment is technically challenging. Especially, precise\r\ncontrol of
microenvironmental properties in vivo is currently not possible. Here, I studied
the\r\nrole of microenvironment geometry in the invasion and detachment of cancer
cells from the\r\nbulk with a simplistic and reductionist approach. In this approach,
I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix
environment, where I was able to\r\nquantitatively tune the geometrical configuration
of the microenvironment and follow tumor\r\ncells with fluorescence live imaging.
To aid quantitative analysis I developed a widely applicable\r\nsoftware application
to automatically analyze and visualize particle tracking data.\r\nQuantitative
analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed
that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent
detachment of cells. These observations correlated with overall higher speed of
cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments
cells preferentially\r\npassed through larger pores, thus invading areas of least
resistance and generating finger-like\r\ninvasive structures. The detachments
occurred mostly at the tips of these structures.\r\nTo investigate the potential
mechanism, we established a two dimensional model to simulate\r\nactive Brownian
particles representing the cell nuclei dynamics. These simulations backed our
in\r\nvitro observations without the need of precise fitting the simulation parameters.
Our model\r\nsuggests the importance of the pore heterogeneity in the direction
perpendicular to the\r\norientation of bias field (lateral heterogeneity), which
causes the interface roughening."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
citation:
ama: Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion.
2022. doi:10.15479/at:ista:12401
apa: Tasciyan, S. (2022). Role of microenvironment heterogeneity in cancer cell
invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12401
chicago: Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell
Invasion.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12401.
ieee: S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,”
Institute of Science and Technology Austria, 2022.
ista: Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion.
Institute of Science and Technology Austria.
mla: Tasciyan, Saren. Role of Microenvironment Heterogeneity in Cancer Cell Invasion.
Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12401.
short: S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion,
Institute of Science and Technology Austria, 2022.
date_created: 2023-01-26T11:55:16Z
date_published: 2022-12-22T00:00:00Z
date_updated: 2023-12-21T23:30:04Z
day: '22'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/at:ista:12401
file:
- access_level: open_access
checksum: cc4a2b4a7e3c4ee8ef7f2dbf909b12bd
content_type: application/pdf
creator: cchlebak
date_created: 2023-01-26T11:58:14Z
date_updated: 2023-12-21T23:30:03Z
embargo: 2023-12-20
file_id: '12402'
file_name: PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf
file_size: 42059787
relation: main_file
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checksum: f1b4ca98b8ab0cb043b1830971e9bd9c
content_type: application/x-zip-compressed
creator: cchlebak
date_created: 2023-01-26T12:00:10Z
date_updated: 2023-12-21T23:30:03Z
embargo_to: open_access
file_id: '12403'
file_name: Source Files - Saren Tasciyan - PhD Thesis.zip
file_size: 261256696
relation: source_file
file_date_updated: 2023-12-21T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '105'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '679'
relation: part_of_dissertation
status: public
- id: '10703'
relation: part_of_dissertation
status: public
- id: '9429'
relation: part_of_dissertation
status: public
- id: '7885'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: Role of microenvironment heterogeneity in cancer cell invasion
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '8988'
abstract:
- lang: eng
text: The differentiation of cells depends on a precise control of their internal
organization, which is the result of a complex dynamic interplay between the cytoskeleton,
molecular motors, signaling molecules, and membranes. For example, in the developing
neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP]
with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite
branching by regulating the small GTPase ARF6. Together with the motor protein
KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol
(3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity.
However, what defines the function of ADAP1 and how its different roles are coordinated
are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions.
We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well
as PI(3,4)P2 act as stop signals for this transport instead of being transported.
We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity
to catalyze GTP hydrolysis by ARF6. Together, our results support a model for
the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters
high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates
from the motor to inactivate ARF6, promoting dendrite branching.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: EM-Fac
acknowledgement: "We thank Urban Bezeljak, Natalia Baranova, Mar Lopez-Pelegrin, Catarina
Alcarva, and Victoria Faas for sharing reagents and helpful discussions. We thank
Veronika Szentirmai for help with protein purifications. We thank Carrie Bernecky,
Sascha Martens, and the M.L. lab for comments on the manuscript. We thank the bioimaging
facility, the life science facility, and Armel Nicolas from the mass spec facility
at the Institute of Science and Technology (IST) Austria for technical support.
C.D. acknowledges funding from the IST fellowship program; this work was supported
by Human Frontier Science Program Young Investigator Grant\r\nRGY0083/2016. "
article_number: e2010054118
article_processing_charge: No
article_type: original
author:
- first_name: Christian F
full_name: Düllberg, Christian F
id: 459064DC-F248-11E8-B48F-1D18A9856A87
last_name: Düllberg
orcid: 0000-0001-6335-9748
- first_name: Albert
full_name: Auer, Albert
id: 3018E8C2-F248-11E8-B48F-1D18A9856A87
last_name: Auer
orcid: 0000-0002-3580-2906
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- first_name: Katrin
full_name: Loibl, Katrin
id: 3760F32C-F248-11E8-B48F-1D18A9856A87
last_name: Loibl
orcid: 0000-0002-2429-7668
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
citation:
ama: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 2021;118(1). doi:10.1073/pnas.2010054118
apa: Düllberg, C. F., Auer, A., Canigova, N., Loibl, K., & Loose, M. (2021).
In vitro reconstitution reveals phosphoinositides as cargo-release factors and
activators of the ARF6 GAP ADAP1. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2010054118
chicago: Düllberg, Christian F, Albert Auer, Nikola Canigova, Katrin Loibl, and
Martin Loose. “In Vitro Reconstitution Reveals Phosphoinositides as Cargo-Release
Factors and Activators of the ARF6 GAP ADAP1.” PNAS. National Academy of
Sciences, 2021. https://doi.org/10.1073/pnas.2010054118.
ieee: C. F. Düllberg, A. Auer, N. Canigova, K. Loibl, and M. Loose, “In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1,” PNAS, vol. 118, no. 1. National Academy of Sciences, 2021.
ista: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. 2021. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 118(1), e2010054118.
mla: Düllberg, Christian F., et al. “In Vitro Reconstitution Reveals Phosphoinositides
as Cargo-Release Factors and Activators of the ARF6 GAP ADAP1.” PNAS, vol.
118, no. 1, e2010054118, National Academy of Sciences, 2021, doi:10.1073/pnas.2010054118.
short: C.F. Düllberg, A. Auer, N. Canigova, K. Loibl, M. Loose, PNAS 118 (2021).
date_created: 2021-01-03T23:01:23Z
date_published: 2021-01-05T00:00:00Z
date_updated: 2023-08-04T11:20:46Z
day: '05'
department:
- _id: MaLo
- _id: MiSi
doi: 10.1073/pnas.2010054118
external_id:
isi:
- '000607270100018'
pmid:
- '33443153'
intvolume: ' 118'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.2010054118
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2599F062-B435-11E9-9278-68D0E5697425
grant_number: RGY0083/2016
name: Reconstitution of cell polarity and axis determination in a cell-free system
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: In vitro reconstitution reveals phosphoinositides as cargo-release factors
and activators of the ARF6 GAP ADAP1
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 118
year: '2021'
...
---
_id: '9259'
abstract:
- lang: eng
text: Gradients of chemokines and growth factors guide migrating cells and morphogenetic
processes. Migration of antigen-presenting dendritic cells from the interstitium
into the lymphatic system is dependent on chemokine CCL21, which is secreted by
endothelial cells of the lymphatic capillary, binds heparan sulfates and forms
gradients decaying into the interstitium. Despite the importance of CCL21 gradients,
and chemokine gradients in general, the mechanisms of gradient formation are unclear.
Studies on fibroblast growth factors have shown that limited diffusion is crucial
for gradient formation. Here, we used the mouse dermis as a model tissue to address
the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the
formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic
endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels
at the lymphatic capillaries and did neither affect interstitial CCL21 gradient
shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan
sulfates at the level of the lymphatic endothelium are dispensable for the formation
of a functional CCL21 gradient.
acknowledgement: "This work was supported by Sigrid Juselius fellowship (KV), University
of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding
(315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the
Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen
is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for
providing the conditional Ext1 mouse strain."
article_number: '630002'
article_processing_charge: No
article_type: original
author:
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Christine
full_name: Moussion, Christine
id: 3356F664-F248-11E8-B48F-1D18A9856A87
last_name: Moussion
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial
chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic
endothelium. Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.630002
apa: Vaahtomeri, K., Moussion, C., Hauschild, R., & Sixt, M. K. (2021). Shape
and function of interstitial chemokine CCL21 gradients are independent of heparan
sulfates produced by lymphatic endothelium. Frontiers in Immunology. Frontiers.
https://doi.org/10.3389/fimmu.2021.630002
chicago: Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt.
“Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent
of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology.
Frontiers, 2021. https://doi.org/10.3389/fimmu.2021.630002.
ieee: K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function
of interstitial chemokine CCL21 gradients are independent of heparan sulfates
produced by lymphatic endothelium,” Frontiers in Immunology, vol. 12. Frontiers,
2021.
ista: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of
interstitial chemokine CCL21 gradients are independent of heparan sulfates produced
by lymphatic endothelium. Frontiers in Immunology. 12, 630002.
mla: Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21
Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.”
Frontiers in Immunology, vol. 12, 630002, Frontiers, 2021, doi:10.3389/fimmu.2021.630002.
short: K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology
12 (2021).
date_created: 2021-03-21T23:01:20Z
date_published: 2021-02-25T00:00:00Z
date_updated: 2023-08-07T14:18:26Z
day: '25'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.3389/fimmu.2021.630002
ec_funded: 1
external_id:
isi:
- '000627134400001'
pmid:
- '33717158'
file:
- access_level: open_access
checksum: 663f5a48375e42afa4bfef58d42ec186
content_type: application/pdf
creator: dernst
date_created: 2021-03-22T12:08:26Z
date_updated: 2021-03-22T12:08:26Z
file_id: '9277'
file_name: 2021_FrontiersImmumo_Vaahtomeri.pdf
file_size: 3740146
relation: main_file
success: 1
file_date_updated: 2021-03-22T12:08:26Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Frontiers in Immunology
publication_identifier:
eissn:
- 1664-3224
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Shape and function of interstitial chemokine CCL21 gradients are independent
of heparan sulfates produced by lymphatic endothelium
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '9294'
abstract:
- lang: eng
text: In this issue of Developmental Cell, Doyle and colleagues identify periodic
anterior contraction as a characteristic feature of fibroblasts and mesenchymal
cancer cells embedded in 3D collagen gels. This contractile mechanism generates
a matrix prestrain required for crawling in fibrous 3D environments.
article_processing_charge: No
article_type: original
author:
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Gärtner FR, Sixt MK. Engaging the front wheels to drive through fibrous terrain.
Developmental Cell. 2021;56(6):723-725. doi:10.1016/j.devcel.2021.03.002
apa: Gärtner, F. R., & Sixt, M. K. (2021). Engaging the front wheels to drive
through fibrous terrain. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2021.03.002
chicago: Gärtner, Florian R, and Michael K Sixt. “Engaging the Front Wheels to Drive
through Fibrous Terrain.” Developmental Cell. Elsevier, 2021. https://doi.org/10.1016/j.devcel.2021.03.002.
ieee: F. R. Gärtner and M. K. Sixt, “Engaging the front wheels to drive through
fibrous terrain,” Developmental Cell, vol. 56, no. 6. Elsevier, pp. 723–725,
2021.
ista: Gärtner FR, Sixt MK. 2021. Engaging the front wheels to drive through fibrous
terrain. Developmental Cell. 56(6), 723–725.
mla: Gärtner, Florian R., and Michael K. Sixt. “Engaging the Front Wheels to Drive
through Fibrous Terrain.” Developmental Cell, vol. 56, no. 6, Elsevier,
2021, pp. 723–25, doi:10.1016/j.devcel.2021.03.002.
short: F.R. Gärtner, M.K. Sixt, Developmental Cell 56 (2021) 723–725.
date_created: 2021-03-28T22:01:41Z
date_published: 2021-03-22T00:00:00Z
date_updated: 2023-08-07T14:26:47Z
day: '22'
department:
- _id: MiSi
doi: 10.1016/j.devcel.2021.03.002
external_id:
isi:
- '000631681200004'
pmid:
- '33756118'
intvolume: ' 56'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.devcel.2021.03.002
month: '03'
oa: 1
oa_version: Published Version
page: 723-725
pmid: 1
publication: Developmental Cell
publication_identifier:
eissn:
- '18781551'
issn:
- '15345807'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Engaging the front wheels to drive through fibrous terrain
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 56
year: '2021'
...
---
_id: '9822'
abstract:
- lang: eng
text: Attachment of adhesive molecules on cell culture surfaces to restrict cell
adhesion to defined areas and shapes has been vital for the progress of in vitro
research. In currently existing patterning methods, a combination of pattern properties
such as stability, precision, specificity, high-throughput outcome, and spatiotemporal
control is highly desirable but challenging to achieve. Here, we introduce a versatile
and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent
patterning step and a subsequent functionalization of the pattern via click chemistry.
This two-step process is feasible on arbitrary surfaces and allows for generation
of sustainable patterns and gradients. The method is validated in different biological
systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining
the growth and migration of cells to the designated areas. We then implement a
sequential photopatterning approach by adding a second switchable patterning step,
allowing for spatiotemporal control over two distinct surface patterns. As a proof
of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis.
Our results show that the spatiotemporal control provided by our “sequential photopatterning”
system is essential for mimicking dynamic biological processes and that our innovative
approach has great potential for further applications in cell science.
acknowledgement: We would like to thank Charlott Leu for the production of our chromium
wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh
Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim
Rädler for his valuable scientific guidance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Themistoklis
full_name: Zisis, Themistoklis
last_name: Zisis
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Miriam
full_name: Balles, Miriam
last_name: Balles
- first_name: Maibritt
full_name: Kretschmer, Maibritt
last_name: Kretschmer
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Janina
full_name: Lange, Janina
last_name: Lange
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Stefan
full_name: Zahler, Stefan
last_name: Zahler
citation:
ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for
studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850
apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R.
P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular
processes under spatiotemporal control. ACS Applied Materials and Interfaces.
American Chemical Society. https://doi.org/10.1021/acsami.1c09850
chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria
Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning
for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied
Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.
ieee: T. Zisis et al., “Sequential and switchable patterning for studying
cellular processes under spatiotemporal control,” ACS Applied Materials and
Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.
ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild
R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning
for studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 13(30), 35545–35560.
mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying
Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and
Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560,
doi:10.1021/acsami.1c09850.
short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait,
R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials
and Interfaces 13 (2021) 35545–35560.
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-08-10T14:22:48Z
day: '04'
ddc:
- '620'
- '570'
department:
- _id: MiSi
- _id: GaTk
- _id: Bio
- _id: CaGu
doi: 10.1021/acsami.1c09850
ec_funded: 1
external_id:
isi:
- '000683741400026'
pmid:
- '34283577'
file:
- access_level: open_access
checksum: b043a91d9f9200e467b970b692687ed3
content_type: application/pdf
creator: asandaue
date_created: 2021-08-09T09:44:03Z
date_updated: 2021-08-09T09:44:03Z
file_id: '9833'
file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf
file_size: 7123293
relation: main_file
success: 1
file_date_updated: 2021-08-09T09:44:03Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '30'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 35545–35560
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: ACS Applied Materials and Interfaces
publication_identifier:
eissn:
- '19448252'
issn:
- '19448244'
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential and switchable patterning for studying cellular processes under
spatiotemporal control
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2021'
...
---
_id: '10834'
abstract:
- lang: eng
text: Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE
regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation
and the protrusion of branched actin filament networks. Moreover, Hem1 loss of
function in immune cells causes autoimmune diseases in humans. Here, we show that
genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis
as well as phagocytic cup formation in addition to defects in lamellipodial protrusion
and migration. Moreover, Hem1-null macrophages displayed strong defects in cell
adhesion despite unaltered podosome formation and concomitant extracellular matrix
degradation. Specifically, dynamics of both adhesion and de-adhesion as well as
concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly
compromised. Accordingly, disruption of WRC function in non-hematopoietic cells
coincided with both defects in adhesion turnover and altered FAK and paxillin
phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished
integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes,
but not lamellipodia formation, were partially rescued by small molecule activation
of FAK. A full rescue of the phenotype, including lamellipodia formation, required
not only the presence of WRCs but also their binding to and activation by Rac.
Collectively, our results uncover that WRC impacts on integrin-dependent processes
in a FAK-dependent manner, controlling formation and dismantling of adhesions,
relevant for properly grabbing onto extracellular surfaces and particles during
cell edge expansion, like in migration or phagocytosis.
acknowledgement: We are grateful to Silvia Prettin, Ina Schleicher, and Petra Hagendorff
for expert technical assistance; David Dettbarn for animal keeping and breeding;
and Lothar Gröbe and Maria Höxter for cell sorting. We also thank Werner Tegge for
peptides and Giorgio Scita for antibodies. This work was supported, in part, by
the Deutsche Forschungsgemeinschaft (DFG), Priority Programm SPP1150 (to T.E.B.S.,
K.R., and M. Sixt), and by DFG grant GRK2223/1 (to K.R.). T.E.B.S. acknowledges
support by the Helmholtz Society through HGF impulse fund W2/W3-066 and M. Schnoor
by the Mexican Council for Science and Technology (CONACyT, 284292 ), Fund SEP-Cinvestav
( 108 ), and the Royal Society, UK (Newton Advanced Fellowship, NAF/R1/180017 ).
article_processing_charge: No
article_type: original
author:
- first_name: Stephanie
full_name: Stahnke, Stephanie
last_name: Stahnke
- first_name: Hermann
full_name: Döring, Hermann
last_name: Döring
- first_name: Charly
full_name: Kusch, Charly
last_name: Kusch
- first_name: David J.J.
full_name: de Gorter, David J.J.
last_name: de Gorter
- first_name: Sebastian
full_name: Dütting, Sebastian
last_name: Dütting
- first_name: Aleks
full_name: Guledani, Aleks
last_name: Guledani
- first_name: Irina
full_name: Pleines, Irina
last_name: Pleines
- first_name: Michael
full_name: Schnoor, Michael
last_name: Schnoor
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Robert
full_name: Geffers, Robert
last_name: Geffers
- first_name: Manfred
full_name: Rohde, Manfred
last_name: Rohde
- first_name: Mathias
full_name: Müsken, Mathias
last_name: Müsken
- first_name: Frieda
full_name: Kage, Frieda
last_name: Kage
- first_name: Anika
full_name: Steffen, Anika
last_name: Steffen
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Bernhard
full_name: Nieswandt, Bernhard
last_name: Nieswandt
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Theresia E.B.
full_name: Stradal, Theresia E.B.
last_name: Stradal
citation:
ama: Stahnke S, Döring H, Kusch C, et al. Loss of Hem1 disrupts macrophage function
and impacts migration, phagocytosis, and integrin-mediated adhesion. Current
Biology. 2021;31(10):2051-2064.e8. doi:10.1016/j.cub.2021.02.043
apa: Stahnke, S., Döring, H., Kusch, C., de Gorter, D. J. J., Dütting, S., Guledani,
A., … Stradal, T. E. B. (2021). Loss of Hem1 disrupts macrophage function and
impacts migration, phagocytosis, and integrin-mediated adhesion. Current Biology.
Elsevier. https://doi.org/10.1016/j.cub.2021.02.043
chicago: Stahnke, Stephanie, Hermann Döring, Charly Kusch, David J.J. de Gorter,
Sebastian Dütting, Aleks Guledani, Irina Pleines, et al. “Loss of Hem1 Disrupts
Macrophage Function and Impacts Migration, Phagocytosis, and Integrin-Mediated
Adhesion.” Current Biology. Elsevier, 2021. https://doi.org/10.1016/j.cub.2021.02.043.
ieee: S. Stahnke et al., “Loss of Hem1 disrupts macrophage function and impacts
migration, phagocytosis, and integrin-mediated adhesion,” Current Biology,
vol. 31, no. 10. Elsevier, p. 2051–2064.e8, 2021.
ista: Stahnke S, Döring H, Kusch C, de Gorter DJJ, Dütting S, Guledani A, Pleines
I, Schnoor M, Sixt MK, Geffers R, Rohde M, Müsken M, Kage F, Steffen A, Faix J,
Nieswandt B, Rottner K, Stradal TEB. 2021. Loss of Hem1 disrupts macrophage function
and impacts migration, phagocytosis, and integrin-mediated adhesion. Current Biology.
31(10), 2051–2064.e8.
mla: Stahnke, Stephanie, et al. “Loss of Hem1 Disrupts Macrophage Function and Impacts
Migration, Phagocytosis, and Integrin-Mediated Adhesion.” Current Biology,
vol. 31, no. 10, Elsevier, 2021, p. 2051–2064.e8, doi:10.1016/j.cub.2021.02.043.
short: S. Stahnke, H. Döring, C. Kusch, D.J.J. de Gorter, S. Dütting, A. Guledani,
I. Pleines, M. Schnoor, M.K. Sixt, R. Geffers, M. Rohde, M. Müsken, F. Kage, A.
Steffen, J. Faix, B. Nieswandt, K. Rottner, T.E.B. Stradal, Current Biology 31
(2021) 2051–2064.e8.
date_created: 2022-03-08T07:51:04Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2023-08-17T07:01:14Z
day: '24'
department:
- _id: MiSi
doi: 10.1016/j.cub.2021.02.043
external_id:
isi:
- '000654652200002'
pmid:
- '33711252'
intvolume: ' 31'
isi: 1
issue: '10'
keyword:
- General Agricultural and Biological Sciences
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.03.24.005835
month: '05'
oa: 1
oa_version: Preprint
page: 2051-2064.e8
pmid: 1
publication: Current Biology
publication_identifier:
issn:
- 0960-9822
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis,
and integrin-mediated adhesion
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 31
year: '2021'
...