---
_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.</jats:p>
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. <i>Science Advances</i>.
    2023;9(3). doi:<a href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>
  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. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>
  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.” <i>Science Advances</i>. American
    Association for the Advancement of Science, 2023. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>.
  ieee: F. Fäßler <i>et al.</i>, “ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning,” <i>Science Advances</i>,
    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.” <i>Science Advances</i>, vol. 9, no.
    3, add6495, American Association for the Advancement of Science, 2023, doi:<a
    href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>.
  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:
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  - 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'
...
---
_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. <i>Biochemical Society
    Transactions</i>. 2023;51(1):87-99. doi:<a href="https://doi.org/10.1042/bst20220221">10.1042/bst20220221</a>
  apa: Fäßler, F., Javoor, M., &#38; Schur, F. K. (2023). Deciphering the molecular
    mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM. <i>Biochemical
    Society Transactions</i>. Portland Press. <a href="https://doi.org/10.1042/bst20220221">https://doi.org/10.1042/bst20220221</a>
  chicago: Fäßler, Florian, Manjunath Javoor, and Florian KM Schur. “Deciphering the
    Molecular Mechanisms of Actin Cytoskeleton Regulation in Cell Migration Using
    Cryo-EM.” <i>Biochemical Society Transactions</i>. Portland Press, 2023. <a href="https://doi.org/10.1042/bst20220221">https://doi.org/10.1042/bst20220221</a>.
  ieee: F. Fäßler, M. Javoor, and F. K. Schur, “Deciphering the molecular mechanisms
    of actin cytoskeleton regulation in cell migration using cryo-EM,” <i>Biochemical
    Society Transactions</i>, 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.” <i>Biochemical Society Transactions</i>,
    vol. 51, no. 1, Portland Press, 2023, pp. 87–99, doi:<a href="https://doi.org/10.1042/bst20220221">10.1042/bst20220221</a>.
  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'
...