---
_id: '9094'
abstract:
- lang: eng
text: Dendritic cells (DCs) are crucial for the priming of naive T cells and the
initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell
contact, the immunological synapse (IS). While it is established that F-actin
dynamics regulates signaling at the T cell side of the contact, little is known
about the cytoskeletal contribution on the DC side. Here, we show that the DC
actin cytoskeleton is decisive for the formation of a multifocal synaptic structure,
which correlates with T cell priming efficiency. DC actin at the IS appears in
transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence
of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase
in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of
activated and proliferating T cells, demonstrating an important role for DC actin
in the regulation of immune synapse functionality.
article_number: e202006081
article_processing_charge: No
article_type: original
author:
- 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: LM
full_name: Altenburger, LM
last_name: Altenburger
- first_name: R
full_name: Hauschild, R
last_name: Hauschild
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: K
full_name: Rottner, K
last_name: Rottner
- first_name: Stradal
full_name: TEB, Stradal
last_name: TEB
- first_name: A
full_name: Diz-Muñoz, A
last_name: Diz-Muñoz
- first_name: JV
full_name: Stein, JV
last_name: Stein
- 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: Leithner AF, Altenburger L, Hauschild R, et al. Dendritic cell actin dynamics
control contact duration and priming efficiency at the immunological synapse.
Journal of Cell Biology. 2021;220(4). doi:10.1083/jcb.202006081
apa: Leithner, A. F., Altenburger, L., Hauschild, R., Assen, F. P., Rottner, K.,
TEB, S., … Sixt, M. K. (2021). Dendritic cell actin dynamics control contact duration
and priming efficiency at the immunological synapse. Journal of Cell Biology.
Rockefeller University Press. https://doi.org/10.1083/jcb.202006081
chicago: Leithner, Alexander F, LM Altenburger, R Hauschild, Frank P Assen, K Rottner,
Stradal TEB, A Diz-Muñoz, JV Stein, and Michael K Sixt. “Dendritic Cell Actin
Dynamics Control Contact Duration and Priming Efficiency at the Immunological
Synapse.” Journal of Cell Biology. Rockefeller University Press, 2021.
https://doi.org/10.1083/jcb.202006081.
ieee: A. F. Leithner et al., “Dendritic cell actin dynamics control contact
duration and priming efficiency at the immunological synapse,” Journal of Cell
Biology, vol. 220, no. 4. Rockefeller University Press, 2021.
ista: Leithner AF, Altenburger L, Hauschild R, Assen FP, Rottner K, TEB S, Diz-Muñoz
A, Stein J, Sixt MK. 2021. Dendritic cell actin dynamics control contact duration
and priming efficiency at the immunological synapse. Journal of Cell Biology.
220(4), e202006081.
mla: Leithner, Alexander F., et al. “Dendritic Cell Actin Dynamics Control Contact
Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell
Biology, vol. 220, no. 4, e202006081, Rockefeller University Press, 2021,
doi:10.1083/jcb.202006081.
short: A.F. Leithner, L. Altenburger, R. Hauschild, F.P. Assen, K. Rottner, S. TEB,
A. Diz-Muñoz, J. Stein, M.K. Sixt, Journal of Cell Biology 220 (2021).
date_created: 2021-02-05T10:08:04Z
date_published: 2021-04-05T00:00:00Z
date_updated: 2023-09-05T13:57:53Z
day: '05'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1083/jcb.202006081
external_id:
isi:
- '000626365700001'
pmid:
- '33533935'
file:
- access_level: open_access
checksum: 843ebc153847c8626e13c9c5ce71d533
content_type: application/pdf
creator: dernst
date_created: 2022-05-12T14:16:21Z
date_updated: 2022-05-12T14:16:21Z
file_id: '11367'
file_name: 2021_JournCellBiology_Leithner.pdf
file_size: 5102328
relation: main_file
success: 1
file_date_updated: 2022-05-12T14:16:21Z
has_accepted_license: '1'
intvolume: ' 220'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
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'
scopus_import: '1'
status: public
title: Dendritic cell actin dynamics control contact duration and priming efficiency
at the immunological synapse
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 220
year: '2021'
...
---
_id: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-03-28T23:30:23Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
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: '10307'
abstract:
- lang: eng
text: Bacteria-host interactions represent a continuous trade-off between benefit
and risk. Thus, the host immune response is faced with a non-trivial problem –
accommodate beneficial commensals and remove harmful pathogens. This is especially
difficult as molecular patterns, such as lipopolysaccharide or specific surface
organelles such as pili, are conserved in both, commensal and pathogenic bacteria.
Type 1 pili, tightly regulated by phase variation, are considered an important
virulence factor of pathogenic bacteria as they facilitate invasion into host
cells. While invasion represents a de facto passive mechanism for pathogens to
escape the host immune response, we demonstrate a fundamental role of type 1 pili
as active modulators of the innate and adaptive immune response.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
citation:
ama: Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021.
doi:10.15479/at:ista:10307
apa: Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307
chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.”
Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.
ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,”
Institute of Science and Technology Austria, 2021.
ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria.
mla: Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.
short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response,
Institute of Science and Technology Austria, 2021.
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-09-07T13:34:38Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
file:
- access_level: open_access
checksum: b39c9e0ef18d0484d537a67551effd02
content_type: application/pdf
creator: ktomasek
date_created: 2021-11-18T15:07:31Z
date_updated: 2022-12-20T23:30:05Z
embargo: 2022-11-18
file_id: '10308'
file_name: ThesisTomasekKathrin.pdf
file_size: 13266088
relation: main_file
- access_level: closed
checksum: c0c440ee9e5ef1102a518a4f9f023e7c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: ktomasek
date_created: 2021-11-18T15:07:46Z
date_updated: 2022-12-20T23:30:05Z
embargo_to: open_access
file_id: '10309'
file_name: ThesisTomasekKathrin.docx
file_size: 7539509
relation: source_file
file_date_updated: 2022-12-20T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '73'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10316'
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: 0000-0002-4561-241X
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: Pathogenic Escherichia coli hijack the host immune response
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_id: '10316'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on dendritic cells as a previously undescribed binding partner of FimH,
the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH
amino acids involved in CD14 binding are highly conserved across pathogenic and
non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced
dendritic cell migration and blunted expression of co-stimulatory molecules, both
rate-limiting factors of T cell activation. While defining an active molecular
mechanism of immune evasion by pathogens, the interaction between FimH and CD14
represents a potential target to interfere with persistent and recurrent infections,
such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra
and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments
and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis.
We thank the IST Austria Scientific Service Units, especially the Bioimaging facility,
the Preclinical facility and the Electron microscopy facility for technical support,
Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions
and Daria Siekhaus for critically reading the manuscript. This work was supported
by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G.,
the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911)
to M.S.
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- 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: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- 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
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv. doi:10.1101/2021.10.18.464770
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2021.10.18.464770
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv, 10.1101/2021.10.18.464770.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2021.10.18.464770.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
BioRxiv (n.d.).
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2024-03-28T23:30:35Z
day: '18'
department:
- _id: CaGu
- _id: MiSi
doi: 10.1101/2021.10.18.464770
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '11843'
relation: later_version
status: public
- id: '10307'
relation: dissertation_contains
status: public
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_id: '7234'
abstract:
- lang: eng
text: T lymphocytes utilize amoeboid migration to navigate effectively within complex
microenvironments. The precise rearrangement of the actin cytoskeleton required
for cellular forward propulsion is mediated by actin regulators, including the
actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates
branched actin filaments at the leading edge. The consequences of modulating Arp2/3
activity on the biophysical properties of the actomyosin cortex and downstream
T cell function are incompletely understood. We report that even a moderate decrease
of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction
in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia
formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by
blebbing migration characterized by transient, balloon‐like protrusions at the
leading edge. Although this migration mode seems to be compatible with interstitial
migration in three‐dimensional environments, diminished locomotion kinetics and
impaired cytotoxicity interfere with optimal T cell function. These findings define
the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity
in cytotoxic effector T lymphocyte activities.
article_processing_charge: No
article_type: original
author:
- first_name: Peyman
full_name: Obeidy, Peyman
last_name: Obeidy
- first_name: Lining A.
full_name: Ju, Lining A.
last_name: Ju
- first_name: Stefan H.
full_name: Oehlers, Stefan H.
last_name: Oehlers
- first_name: Nursafwana S.
full_name: Zulkhernain, Nursafwana S.
last_name: Zulkhernain
- first_name: Quintin
full_name: Lee, Quintin
last_name: Lee
- first_name: Jorge L.
full_name: Galeano Niño, Jorge L.
last_name: Galeano Niño
- first_name: Rain Y.Q.
full_name: Kwan, Rain Y.Q.
last_name: Kwan
- first_name: Shweta
full_name: Tikoo, Shweta
last_name: Tikoo
- first_name: Lois L.
full_name: Cavanagh, Lois L.
last_name: Cavanagh
- first_name: Paulus
full_name: Mrass, Paulus
last_name: Mrass
- first_name: Adam J.L.
full_name: Cook, Adam J.L.
last_name: Cook
- first_name: Shaun P.
full_name: Jackson, Shaun P.
last_name: Jackson
- first_name: Maté
full_name: Biro, Maté
last_name: Biro
- first_name: Ben
full_name: Roediger, Ben
last_name: Roediger
- 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: Wolfgang
full_name: Weninger, Wolfgang
last_name: Weninger
citation:
ama: Obeidy P, Ju LA, Oehlers SH, et al. Partial loss of actin nucleator actin-related
protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology
and Cell Biology. 2020;98(2):93-113. doi:10.1111/imcb.12304
apa: Obeidy, P., Ju, L. A., Oehlers, S. H., Zulkhernain, N. S., Lee, Q., Galeano
Niño, J. L., … Weninger, W. (2020). Partial loss of actin nucleator actin-related
protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology
and Cell Biology. Wiley. https://doi.org/10.1111/imcb.12304
chicago: Obeidy, Peyman, Lining A. Ju, Stefan H. Oehlers, Nursafwana S. Zulkhernain,
Quintin Lee, Jorge L. Galeano Niño, Rain Y.Q. Kwan, et al. “Partial Loss of Actin
Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.”
Immunology and Cell Biology. Wiley, 2020. https://doi.org/10.1111/imcb.12304.
ieee: P. Obeidy et al., “Partial loss of actin nucleator actin-related protein
2/3 activity triggers blebbing in primary T lymphocytes,” Immunology and Cell
Biology, vol. 98, no. 2. Wiley, pp. 93–113, 2020.
ista: Obeidy P, Ju LA, Oehlers SH, Zulkhernain NS, Lee Q, Galeano Niño JL, Kwan
RYQ, Tikoo S, Cavanagh LL, Mrass P, Cook AJL, Jackson SP, Biro M, Roediger B,
Sixt MK, Weninger W. 2020. Partial loss of actin nucleator actin-related protein
2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology.
98(2), 93–113.
mla: Obeidy, Peyman, et al. “Partial Loss of Actin Nucleator Actin-Related Protein
2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell
Biology, vol. 98, no. 2, Wiley, 2020, pp. 93–113, doi:10.1111/imcb.12304.
short: P. Obeidy, L.A. Ju, S.H. Oehlers, N.S. Zulkhernain, Q. Lee, J.L. Galeano
Niño, R.Y.Q. Kwan, S. Tikoo, L.L. Cavanagh, P. Mrass, A.J.L. Cook, S.P. Jackson,
M. Biro, B. Roediger, M.K. Sixt, W. Weninger, Immunology and Cell Biology 98 (2020)
93–113.
date_created: 2020-01-05T23:00:48Z
date_published: 2020-02-01T00:00:00Z
date_updated: 2023-08-17T14:21:12Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1111/imcb.12304
external_id:
isi:
- '000503885600001'
pmid:
- '31698518'
file:
- access_level: open_access
checksum: c389477b4b52172ef76afff8a06c6775
content_type: application/pdf
creator: dernst
date_created: 2020-11-19T11:22:33Z
date_updated: 2020-11-19T11:22:33Z
file_id: '8775'
file_name: 2020_ImmunologyCellBio_Obeidy.pdf
file_size: 8569945
relation: main_file
success: 1
file_date_updated: 2020-11-19T11:22:33Z
has_accepted_license: '1'
intvolume: ' 98'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 93-113
pmid: 1
publication: Immunology and Cell Biology
publication_identifier:
eissn:
- '14401711'
issn:
- '08189641'
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Partial loss of actin nucleator actin-related protein 2/3 activity triggers
blebbing in primary T lymphocytes
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: 98
year: '2020'
...
---
_id: '7623'
abstract:
- lang: eng
text: A two-dimensional mathematical model for cells migrating without adhesion
capabilities is presented and analyzed. Cells are represented by their cortex,
which is modeled as an elastic curve, subject to an internal pressure force. Net
polymerization or depolymerization in the cortex is modeled via local addition
or removal of material, driving a cortical flow. The model takes the form of a
fully nonlinear degenerate parabolic system. An existence analysis is carried
out by adapting ideas from the theory of gradient flows. Numerical simulations
show that these simple rules can account for the behavior observed in experiments,
suggesting a possible mechanical mechanism for adhesion-independent motility.
acknowledgement: This work has been supported by the Vienna Science and Technology
Fund, Grant no. LS13-029. G.J. and C.S. also acknowledge support by the Austrian
Science Fund, Grants no. W1245, F 65, and W1261, as well as by the Fondation Sciences
Mathématiques de Paris, and by Paris-Sciences-et-Lettres.
article_processing_charge: No
article_type: original
author:
- first_name: Gaspard
full_name: Jankowiak, Gaspard
last_name: Jankowiak
- first_name: Diane
full_name: Peurichard, Diane
last_name: Peurichard
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Christian
full_name: Schmeiser, Christian
last_name: Schmeiser
- 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: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. Modeling adhesion-independent
cell migration. Mathematical Models and Methods in Applied Sciences. 2020;30(3):513-537.
doi:10.1142/S021820252050013X
apa: Jankowiak, G., Peurichard, D., Reversat, A., Schmeiser, C., & Sixt, M.
K. (2020). Modeling adhesion-independent cell migration. Mathematical Models
and Methods in Applied Sciences. World Scientific. https://doi.org/10.1142/S021820252050013X
chicago: Jankowiak, Gaspard, Diane Peurichard, Anne Reversat, Christian Schmeiser,
and Michael K Sixt. “Modeling Adhesion-Independent Cell Migration.” Mathematical
Models and Methods in Applied Sciences. World Scientific, 2020. https://doi.org/10.1142/S021820252050013X.
ieee: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, and M. K. Sixt, “Modeling
adhesion-independent cell migration,” Mathematical Models and Methods in Applied
Sciences, vol. 30, no. 3. World Scientific, pp. 513–537, 2020.
ista: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. 2020. Modeling
adhesion-independent cell migration. Mathematical Models and Methods in Applied
Sciences. 30(3), 513–537.
mla: Jankowiak, Gaspard, et al. “Modeling Adhesion-Independent Cell Migration.”
Mathematical Models and Methods in Applied Sciences, vol. 30, no. 3, World
Scientific, 2020, pp. 513–37, doi:10.1142/S021820252050013X.
short: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, M.K. Sixt, Mathematical
Models and Methods in Applied Sciences 30 (2020) 513–537.
date_created: 2020-03-31T11:25:05Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2023-08-18T10:18:56Z
day: '18'
department:
- _id: MiSi
doi: 10.1142/S021820252050013X
external_id:
arxiv:
- '1903.09426'
isi:
- '000525349900003'
intvolume: ' 30'
isi: 1
issue: '3'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1903.09426
month: '03'
oa: 1
oa_version: Preprint
page: 513-537
project:
- _id: 25AD6156-B435-11E9-9278-68D0E5697425
grant_number: LS13-029
name: Modeling of Polarization and Motility of Leukocytes in Three-Dimensional Environments
publication: Mathematical Models and Methods in Applied Sciences
publication_identifier:
issn:
- '02182025'
publication_status: published
publisher: World Scientific
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modeling adhesion-independent cell migration
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 30
year: '2020'
...
---
_id: '7875'
abstract:
- lang: eng
text: 'Cells navigating through complex tissues face a fundamental challenge: while
multiple protrusions explore different paths, the cell needs to avoid entanglement.
How a cell surveys and then corrects its own shape is poorly understood. Here,
we demonstrate that spatially distinct microtubule dynamics regulate amoeboid
cell migration by locally promoting the retraction of protrusions. In migrating
dendritic cells, local microtubule depolymerization within protrusions remote
from the microtubule organizing center triggers actomyosin contractility controlled
by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin
localization, thereby causing two effects that rate-limit locomotion: (1) impaired
cell edge coordination during path finding and (2) defective adhesion resolution.
Compromised shape control is particularly hindering in geometrically complex microenvironments,
where it leads to entanglement and ultimately fragmentation of the cell body.
We thus demonstrate that microtubules can act as a proprioceptive device: they
sense cell shape and control actomyosin retraction to sustain cellular coherence.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (Life Sciences, Bioimaging,
Preclinical) of the Institute of Science and Technology Austria for excellent support.
This work was funded by the European Research Council (ERC StG 281556 and CoG 724373),
two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20
to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O.
Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from
the People Program (Marie Curie Actions) of the European Union’s Seventh Framework
Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734)
and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014)
co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier
by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s
Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian
Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and
Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry
of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European
Funds for Social and Regional Development."
article_number: e201907154
article_processing_charge: No
article_type: original
author:
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Irute
full_name: Girkontaite, Irute
last_name: Girkontaite
- first_name: Kerry
full_name: Tedford, Kerry
last_name: Tedford
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Oliver
full_name: Thorn-Seshold, Oliver
last_name: Thorn-Seshold
- first_name: Dirk
full_name: Trauner, Dirk
id: E8F27F48-3EBA-11E9-92A1-B709E6697425
last_name: Trauner
- first_name: Hans
full_name: Häcker, Hans
last_name: Häcker
- first_name: Klaus Dieter
full_name: Fischer, Klaus Dieter
last_name: Fischer
- first_name: Eva
full_name: Kiermaier, Eva
id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
last_name: Kiermaier
orcid: 0000-0001-6165-5738
- 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: Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape
and coherence in amoeboid migrating cells. The Journal of Cell Biology.
2020;219(6). doi:10.1083/jcb.201907154
apa: Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin,
J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in
amoeboid migrating cells. The Journal of Cell Biology. Rockefeller University
Press. https://doi.org/10.1083/jcb.201907154
chicago: Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry
Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular
Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology.
Rockefeller University Press, 2020. https://doi.org/10.1083/jcb.201907154.
ieee: A. Kopf et al., “Microtubules control cellular shape and coherence
in amoeboid migrating cells,” The Journal of Cell Biology, vol. 219, no.
6. Rockefeller University Press, 2020.
ista: Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold
O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control
cellular shape and coherence in amoeboid migrating cells. The Journal of Cell
Biology. 219(6), e201907154.
mla: Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in
Amoeboid Migrating Cells.” The Journal of Cell Biology, vol. 219, no. 6,
e201907154, Rockefeller University Press, 2020, doi:10.1083/jcb.201907154.
short: A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin,
O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt,
The Journal of Cell Biology 219 (2020).
date_created: 2020-05-24T22:00:56Z
date_published: 2020-06-01T00:00:00Z
date_updated: 2023-08-21T06:28:17Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1083/jcb.201907154
ec_funded: 1
external_id:
isi:
- '000538141100020'
pmid:
- '32379884'
file:
- access_level: open_access
checksum: cb0b9c77842ae1214caade7b77e4d82d
content_type: application/pdf
creator: dernst
date_created: 2020-11-24T13:25:13Z
date_updated: 2020-11-24T13:25:13Z
file_id: '8801'
file_name: 2020_JCellBiol_Kopf.pdf
file_size: 7536712
relation: main_file
success: 1
file_date_updated: 2020-11-24T13:25:13Z
has_accepted_license: '1'
intvolume: ' 219'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
- _id: 252C3B08-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W 1250-B20
name: Nano-Analytics of Cellular Systems
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1396-2014
name: Molecular and system level view of immune cell migration
publication: The Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubules control cellular shape and coherence in amoeboid migrating cells
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: 219
year: '2020'
...
---
_id: '7876'
abstract:
- lang: eng
text: 'In contrast to lymph nodes, the lymphoid regions of the spleen—the white
pulp—are located deep within the organ, yielding the trafficking paths of T cells
in the white pulp largely invisible. In an intravital microscopy tour de force
reported in this issue of Immunity, Chauveau et al. show that T cells perform
unidirectional, perivascular migration through the enigmatic marginal zone bridging
channels. '
article_processing_charge: No
article_type: original
author:
- 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: Tim
full_name: Lämmermann, Tim
last_name: Lämmermann
citation:
ama: 'Sixt MK, Lämmermann T. T cells: Bridge-and-channel commute to the white pulp.
Immunity. 2020;52(5):721-723. doi:10.1016/j.immuni.2020.04.020'
apa: 'Sixt, M. K., & Lämmermann, T. (2020). T cells: Bridge-and-channel commute
to the white pulp. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2020.04.020'
chicago: 'Sixt, Michael K, and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute
to the White Pulp.” Immunity. Elsevier, 2020. https://doi.org/10.1016/j.immuni.2020.04.020.'
ieee: 'M. K. Sixt and T. Lämmermann, “T cells: Bridge-and-channel commute to the
white pulp,” Immunity, vol. 52, no. 5. Elsevier, pp. 721–723, 2020.'
ista: 'Sixt MK, Lämmermann T. 2020. T cells: Bridge-and-channel commute to the white
pulp. Immunity. 52(5), 721–723.'
mla: 'Sixt, Michael K., and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute
to the White Pulp.” Immunity, vol. 52, no. 5, Elsevier, 2020, pp. 721–23,
doi:10.1016/j.immuni.2020.04.020.'
short: M.K. Sixt, T. Lämmermann, Immunity 52 (2020) 721–723.
date_created: 2020-05-24T22:00:57Z
date_published: 2020-05-19T00:00:00Z
date_updated: 2023-08-21T06:27:18Z
day: '19'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2020.04.020
external_id:
isi:
- '000535371100002'
intvolume: ' 52'
isi: 1
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://pure.mpg.de/pubman/item/item_3265599_2/component/file_3265620/Sixt%20et%20al..pdf
month: '05'
oa: 1
oa_version: Published Version
page: 721-723
publication: Immunity
publication_identifier:
eissn:
- '10974180'
issn:
- '10747613'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'T cells: Bridge-and-channel commute to the white pulp'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 52
year: '2020'
...
---
_id: '7909'
abstract:
- lang: eng
text: Cell migration entails networks and bundles of actin filaments termed lamellipodia
and microspikes or filopodia, respectively, as well as focal adhesions, all of
which recruit Ena/VASP family members hitherto thought to antagonize efficient
cell motility. However, we find these proteins to act as positive regulators of
migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP
proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture,
as evidenced by changed network geometry as well as reduction of filament length
and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping
protein accumulation. Loss of Ena/VASP function also abolished the formation of
microspikes normally embedded in lamellipodia, but not of filopodia capable of
emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated
adhesion accompanied by reduced traction forces exerted through these structures.
Our data thus uncover novel Ena/VASP functions of these actin polymerases that
are fully consistent with their promotion of cell migration.
article_number: e55351
article_processing_charge: No
article_type: original
author:
- first_name: Julia
full_name: Damiano-Guercio, Julia
last_name: Damiano-Guercio
- first_name: Laëtitia
full_name: Kurzawa, Laëtitia
last_name: Kurzawa
- first_name: Jan
full_name: Müller, Jan
id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D
last_name: Müller
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Matthias
full_name: Schaks, Matthias
last_name: Schaks
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- first_name: Thomas
full_name: Pokrant, Thomas
last_name: Pokrant
- first_name: Stefan
full_name: Brühmann, Stefan
last_name: Brühmann
- first_name: Joern
full_name: Linkner, Joern
last_name: Linkner
- first_name: Laurent
full_name: Blanchoin, Laurent
last_name: Blanchoin
- 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: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
citation:
ama: Damiano-Guercio J, Kurzawa L, Müller J, et al. Loss of Ena/VASP interferes
with lamellipodium architecture, motility and integrin-dependent adhesion. eLife.
2020;9. doi:10.7554/eLife.55351
apa: Damiano-Guercio, J., Kurzawa, L., Müller, J., Dimchev, G. A., Schaks, M., Nemethova,
M., … Faix, J. (2020). Loss of Ena/VASP interferes with lamellipodium architecture,
motility and integrin-dependent adhesion. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.55351
chicago: Damiano-Guercio, Julia, Laëtitia Kurzawa, Jan Müller, Georgi A Dimchev,
Matthias Schaks, Maria Nemethova, Thomas Pokrant, et al. “Loss of Ena/VASP Interferes
with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” ELife.
eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.55351.
ieee: J. Damiano-Guercio et al., “Loss of Ena/VASP interferes with lamellipodium
architecture, motility and integrin-dependent adhesion,” eLife, vol. 9.
eLife Sciences Publications, 2020.
ista: Damiano-Guercio J, Kurzawa L, Müller J, Dimchev GA, Schaks M, Nemethova M,
Pokrant T, Brühmann S, Linkner J, Blanchoin L, Sixt MK, Rottner K, Faix J. 2020.
Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent
adhesion. eLife. 9, e55351.
mla: Damiano-Guercio, Julia, et al. “Loss of Ena/VASP Interferes with Lamellipodium
Architecture, Motility and Integrin-Dependent Adhesion.” ELife, vol. 9,
e55351, eLife Sciences Publications, 2020, doi:10.7554/eLife.55351.
short: J. Damiano-Guercio, L. Kurzawa, J. Müller, G.A. Dimchev, M. Schaks, M. Nemethova,
T. Pokrant, S. Brühmann, J. Linkner, L. Blanchoin, M.K. Sixt, K. Rottner, J. Faix,
ELife 9 (2020).
date_created: 2020-05-31T22:00:49Z
date_published: 2020-05-11T00:00:00Z
date_updated: 2023-08-21T06:32:25Z
day: '11'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.7554/eLife.55351
ec_funded: 1
external_id:
isi:
- '000537208000001'
file:
- access_level: open_access
checksum: d33bd4441b9a0195718ce1ba5d2c48a6
content_type: application/pdf
creator: dernst
date_created: 2020-06-02T10:35:37Z
date_updated: 2020-07-14T12:48:05Z
file_id: '7914'
file_name: 2020_eLife_Damiano_Guercio.pdf
file_size: 10535713
relation: main_file
file_date_updated: 2020-07-14T12:48:05Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: eLife
publication_identifier:
eissn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent
adhesion
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: 9
year: '2020'
...
---
_id: '8132'
abstract:
- lang: eng
text: The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral
branched actin network constituting one of the main drivers of eukaryotic cell
migration. Here, we uncover an essential role of the hematopoietic-specific WRC
component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies
an inborn error of immunity with systemic autoimmunity, at cellular level marked
by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia.
Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In
the absence of Hem1, B cells become deprived of extracellular stimuli necessary
to maintain the strength of B cell receptor signaling at a level permissive for
survival of non-autoreactive B cells. This shifts the balance of B cell fate choices
toward autoreactive B cells and thus autoimmunity.
article_number: eabc3979
article_processing_charge: No
article_type: original
author:
- first_name: Elisabeth
full_name: Salzer, Elisabeth
last_name: Salzer
- first_name: Samaneh
full_name: Zoghi, Samaneh
last_name: Zoghi
- first_name: Máté G.
full_name: Kiss, Máté G.
last_name: Kiss
- first_name: Frieda
full_name: Kage, Frieda
last_name: Kage
- first_name: Christina
full_name: Rashkova, Christina
last_name: Rashkova
- first_name: Stephanie
full_name: Stahnke, Stephanie
last_name: Stahnke
- first_name: Matthias
full_name: Haimel, Matthias
last_name: Haimel
- first_name: René
full_name: Platzer, René
last_name: Platzer
- first_name: Michael
full_name: Caldera, Michael
last_name: Caldera
- first_name: Rico Chandra
full_name: Ardy, Rico Chandra
last_name: Ardy
- first_name: Birgit
full_name: Hoeger, Birgit
last_name: Hoeger
- first_name: Jana
full_name: Block, Jana
last_name: Block
- first_name: David
full_name: Medgyesi, David
last_name: Medgyesi
- first_name: Celine
full_name: Sin, Celine
last_name: Sin
- first_name: Sepideh
full_name: Shahkarami, Sepideh
last_name: Shahkarami
- first_name: Renate
full_name: Kain, Renate
last_name: Kain
- first_name: Vahid
full_name: Ziaee, Vahid
last_name: Ziaee
- first_name: Peter
full_name: Hammerl, Peter
last_name: Hammerl
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Loïc
full_name: Dupré, Loïc
last_name: Dupré
- first_name: Johannes B.
full_name: Huppa, Johannes B.
last_name: Huppa
- 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: Alexis
full_name: Lomakin, Alexis
last_name: Lomakin
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Christoph J.
full_name: Binder, Christoph J.
last_name: Binder
- first_name: Theresia E.B.
full_name: Stradal, Theresia E.B.
last_name: Stradal
- first_name: Nima
full_name: Rezaei, Nima
last_name: Rezaei
- first_name: Kaan
full_name: Boztug, Kaan
last_name: Boztug
citation:
ama: Salzer E, Zoghi S, Kiss MG, et al. The cytoskeletal regulator HEM1 governs
B cell development and prevents autoimmunity. Science Immunology. 2020;5(49).
doi:10.1126/sciimmunol.abc3979
apa: Salzer, E., Zoghi, S., Kiss, M. G., Kage, F., Rashkova, C., Stahnke, S., …
Boztug, K. (2020). The cytoskeletal regulator HEM1 governs B cell development
and prevents autoimmunity. Science Immunology. AAAS. https://doi.org/10.1126/sciimmunol.abc3979
chicago: Salzer, Elisabeth, Samaneh Zoghi, Máté G. Kiss, Frieda Kage, Christina
Rashkova, Stephanie Stahnke, Matthias Haimel, et al. “The Cytoskeletal Regulator
HEM1 Governs B Cell Development and Prevents Autoimmunity.” Science Immunology.
AAAS, 2020. https://doi.org/10.1126/sciimmunol.abc3979.
ieee: E. Salzer et al., “The cytoskeletal regulator HEM1 governs B cell development
and prevents autoimmunity,” Science Immunology, vol. 5, no. 49. AAAS, 2020.
ista: Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, Haimel M, Platzer
R, Caldera M, Ardy RC, Hoeger B, Block J, Medgyesi D, Sin C, Shahkarami S, Kain
R, Ziaee V, Hammerl P, Bock C, Menche J, Dupré L, Huppa JB, Sixt MK, Lomakin A,
Rottner K, Binder CJ, Stradal TEB, Rezaei N, Boztug K. 2020. The cytoskeletal
regulator HEM1 governs B cell development and prevents autoimmunity. Science Immunology.
5(49), eabc3979.
mla: Salzer, Elisabeth, et al. “The Cytoskeletal Regulator HEM1 Governs B Cell Development
and Prevents Autoimmunity.” Science Immunology, vol. 5, no. 49, eabc3979,
AAAS, 2020, doi:10.1126/sciimmunol.abc3979.
short: E. Salzer, S. Zoghi, M.G. Kiss, F. Kage, C. Rashkova, S. Stahnke, M. Haimel,
R. Platzer, M. Caldera, R.C. Ardy, B. Hoeger, J. Block, D. Medgyesi, C. Sin, S.
Shahkarami, R. Kain, V. Ziaee, P. Hammerl, C. Bock, J. Menche, L. Dupré, J.B.
Huppa, M.K. Sixt, A. Lomakin, K. Rottner, C.J. Binder, T.E.B. Stradal, N. Rezaei,
K. Boztug, Science Immunology 5 (2020).
date_created: 2020-07-19T22:00:58Z
date_published: 2020-07-10T00:00:00Z
date_updated: 2023-08-22T07:56:04Z
day: '10'
department:
- _id: MiSi
doi: 10.1126/sciimmunol.abc3979
external_id:
isi:
- '000546994600004'
pmid:
- '32646852'
intvolume: ' 5'
isi: 1
issue: '49'
language:
- iso: eng
month: '07'
oa_version: None
pmid: 1
publication: Science Immunology
publication_identifier:
eissn:
- '24709468'
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2020'
...