---
_id: '12421'
abstract:
- lang: eng
text: The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics
in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble
in a spatiotemporally controlled manner allows it to form higher-order structures,
which can generate forces required for a cell to explore and navigate through
its environment. It is regulated not only via a complex synergistic and competitive
interplay between actin-binding proteins (ABP), but also by filament biochemistry
and filament geometry. The lack of structural insights into how geometry and ABPs
regulate the actin cytoskeleton limits our understanding of the molecular mechanisms
that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration
characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced
computational methods, it is now possible to define these molecular mechanisms
involving actin and its interactors at both atomic and ultra-structural levels
in vitro and in cellulo. In this review, we will provide an overview of the available
cryo-EM methods, applicable to further our understanding of the actin cytoskeleton,
specifically in the context of cell migration. We will discuss how these methods
have been employed to elucidate ABP- and geometry-defined regulatory mechanisms
in initiating, maintaining, and disassembling cellular actin networks in migratory
protrusions.
acknowledgement: 'We apologize for not being able to mention and cite additional excellent
work that would have fit the scope of this review, due to space restraints. We thank
Jesse Hansen for comments on the manuscript. We acknowledge support from the Austrian
Science Fund (FWF): P33367 and the Institute of Science and Technology Austria.'
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Manjunath
full_name: Javoor, Manjunath
id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
last_name: Javoor
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Javoor M, Schur FK. Deciphering the molecular mechanisms of actin
cytoskeleton regulation in cell migration using cryo-EM. Biochemical Society
Transactions. 2023;51(1):87-99. doi:10.1042/bst20220221
apa: Fäßler, F., Javoor, M., & Schur, F. K. (2023). Deciphering the molecular
mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM. Biochemical
Society Transactions. Portland Press. https://doi.org/10.1042/bst20220221
chicago: Fäßler, Florian, Manjunath Javoor, and Florian KM Schur. “Deciphering the
Molecular Mechanisms of Actin Cytoskeleton Regulation in Cell Migration Using
Cryo-EM.” Biochemical Society Transactions. Portland Press, 2023. https://doi.org/10.1042/bst20220221.
ieee: F. Fäßler, M. Javoor, and F. K. Schur, “Deciphering the molecular mechanisms
of actin cytoskeleton regulation in cell migration using cryo-EM,” Biochemical
Society Transactions, vol. 51, no. 1. Portland Press, pp. 87–99, 2023.
ista: Fäßler F, Javoor M, Schur FK. 2023. Deciphering the molecular mechanisms of
actin cytoskeleton regulation in cell migration using cryo-EM. Biochemical Society
Transactions. 51(1), 87–99.
mla: Fäßler, Florian, et al. “Deciphering the Molecular Mechanisms of Actin Cytoskeleton
Regulation in Cell Migration Using Cryo-EM.” Biochemical Society Transactions,
vol. 51, no. 1, Portland Press, 2023, pp. 87–99, doi:10.1042/bst20220221.
short: F. Fäßler, M. Javoor, F.K. Schur, Biochemical Society Transactions 51 (2023)
87–99.
date_created: 2023-01-27T10:08:19Z
date_published: 2023-02-01T00:00:00Z
date_updated: 2023-08-01T12:55:32Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1042/bst20220221
external_id:
isi:
- '000926043100001'
file:
- access_level: open_access
checksum: 4e7069845e3dad22bb44fb71ec624c60
content_type: application/pdf
creator: dernst
date_created: 2023-03-16T07:58:16Z
date_updated: 2023-03-16T07:58:16Z
file_id: '12728'
file_name: 2023_BioChemicalSocietyTransactions_Faessler.pdf
file_size: 10045006
relation: main_file
success: 1
file_date_updated: 2023-03-16T07:58:16Z
has_accepted_license: '1'
intvolume: ' 51'
isi: 1
issue: '1'
keyword:
- Biochemistry
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 87-99
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
publication: Biochemical Society Transactions
publication_identifier:
eissn:
- 1470-8752
issn:
- 0300-5127
publication_status: published
publisher: Portland Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell
migration using cryo-EM
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: 51
year: '2023'
...
---
_id: '12334'
abstract:
- lang: eng
text: Regulation of the Arp2/3 complex is required for productive nucleation of
branched actin networks. An emerging aspect of regulation is the incorporation
of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit
isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity
and branch junction stability. We have combined reverse genetics and cellular
structural biology to describe how ArpC5 and ArpC5L differentially affect cell
migration. Both define the structural stability of ArpC1 in branch junctions and,
in turn, by determining protrusion characteristics, affect protein dynamics and
actin network ultrastructure. ArpC5 isoforms also affect the positioning of members
of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament
elongators, which mediate ArpC5 isoform–specific effects on the actin assembly
level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling
pathway enhancing cell migration.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: "We would like to thank K. von Peinen and B. Denker (Helmholtz Centre
for Infection Research, Braunschweig, Germany) for experimental and technical assistance,
respectively.\r\nThis research was supported by the Scientific Service Units (SSUs)
of ISTA through resources provided by Scientific Computing (SciComp), the Life Science
Facility (LSF), the Imaging and Optics facility (IOF), and the Electron Microscopy
Facility (EMF). We acknowledge support from ISTA and from the Austrian Science Fund
(FWF) (P33367) to F.K.M.S., from the Research Training Group GRK2223 and the Helmholtz
Society to K.R,. and from the Deutsche Forschungsgemeinschaft (DFG) to J.F. and
K.R."
article_number: add6495
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Manjunath
full_name: Javoor, Manjunath
id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
last_name: Javoor
- first_name: Julia
full_name: Datler, Julia
id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
last_name: Datler
orcid: 0000-0002-3616-8580
- first_name: Hermann
full_name: Döring, Hermann
last_name: Döring
- first_name: Florian
full_name: Hofer, Florian
id: b9d234ba-9e33-11ed-95b6-cd561df280e6
last_name: Hofer
- 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: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Javoor M, Datler J, et al. ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning. Science Advances.
2023;9(3). doi:10.1126/sciadv.add6495
apa: Fäßler, F., Javoor, M., Datler, J., Döring, H., Hofer, F., Dimchev, G. A.,
… Schur, F. K. (2023). ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion
through differential Ena/VASP positioning. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.add6495
chicago: Fäßler, Florian, Manjunath Javoor, Julia Datler, Hermann Döring, Florian
Hofer, Georgi A Dimchev, Victor-Valentin Hodirnau, Jan Faix, Klemens Rottner,
and Florian KM Schur. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
through Differential Ena/VASP Positioning.” Science Advances. American
Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciadv.add6495.
ieee: F. Fäßler et al., “ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning,” Science Advances,
vol. 9, no. 3. American Association for the Advancement of Science, 2023.
ista: Fäßler F, Javoor M, Datler J, Döring H, Hofer F, Dimchev GA, Hodirnau V-V,
Faix J, Rottner K, Schur FK. 2023. ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning. Science Advances. 9(3),
add6495.
mla: Fäßler, Florian, et al. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
through Differential Ena/VASP Positioning.” Science Advances, vol. 9, no.
3, add6495, American Association for the Advancement of Science, 2023, doi:10.1126/sciadv.add6495.
short: F. Fäßler, M. Javoor, J. Datler, H. Döring, F. Hofer, G.A. Dimchev, V.-V.
Hodirnau, J. Faix, K. Rottner, F.K. Schur, Science Advances 9 (2023).
date_created: 2023-01-23T07:26:42Z
date_published: 2023-01-20T00:00:00Z
date_updated: 2023-11-21T08:05:35Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1126/sciadv.add6495
external_id:
isi:
- '000964550100015'
file:
- access_level: open_access
checksum: ce81a6d0b84170e5e8c62f6acfa15d9e
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T07:45:54Z
date_updated: 2023-01-23T07:45:54Z
file_id: '12335'
file_name: 2023_ScienceAdvances_Faessler.pdf
file_size: 1756234
relation: main_file
success: 1
file_date_updated: 2023-01-23T07:45:54Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '3'
keyword:
- Multidisciplinary
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
record:
- id: '14562'
relation: research_data
status: public
scopus_import: '1'
status: public
title: ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential
Ena/VASP positioning
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2023'
...