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Cited by 40Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingProtein Structure and Dynamics

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Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament

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Liu, Tianyang, Cao, Luyan, Mladenov, Miroslav, Jegou, Antoine, Way, Michael, Moores, Carolyn A.·2024·Nature Structural & Molecular Biology
DOI 10.1038/s41594-023-01205-2PMC PMC11102864

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Abstract

Regulation of the assembly and turnover of branched actin filament networks nucleated by the Arp2/3 complex is essential during many cellular processes, including cell migration and membrane trafficking. Cortactin is important for actin branch stabilization, but the mechanism by which this occurs is unclear. Given this, we determined the structure of vertebrate cortactin-stabilized Arp2/3 actin branches using cryogenic electron microscopy. We find that cortactin interacts with the new daughter filament nucleated by the Arp2/3 complex at the branch site, rather than the initial mother actin filament. Cortactin preferentially binds activated Arp3. It also stabilizes the F-actin-like interface of activated Arp3 with the first actin subunit of the new filament, and its central repeats extend along successive daughter-filament subunits. The preference of cortactin for activated Arp3 explains its retention at the actin branch and accounts for its synergy with other nucleation-promoting factors in regulating branched actin network dynamics.

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Metadata

Authors
Liu, T., Cao, L., Mladenov, M., Jegou, A., Way, M., & Moores, C. A.
Affiliations
  • Institute of Structural and Molecular Biology (GB)
  • The Francis Crick Institute (GB)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Way, Michael
  • Moores, Carolyn A.
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2024-01-24
Volume
31
Issue
5
Pages
801-809
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-023-01205-2
PMC
PMC11102864
OpenAlex
W4391169059
Cited by
40
References
71
Citations by year
2026: 9 · 2025: 22 · 2024: 8
FWCI
8.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc)
Funders
  • Wellcome Trust (CC2096, 202679/Z/16/Z, Z/17/Z, 202679, 206166/Z/17/Z, 206166)
  • Francis Crick Institute (CC2096)
  • Cancer Research UK (CC2096)
  • European Commission (HORIZON2020, H2020, H2020‐MSCA‐IF, 101028239, 810207, H2020-MSCA)
  • University of Glasgow
  • Horizon 2020 Framework Programme (H2020-MSCA, 810207)
  • Medical Research Council (CC2096)
  • Birkbeck, University of London
  • H2020 European Research Council (679116)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
cortactin, Arp2/3 complex, branched actin networks, actin nucleation, actin cytoskeleton dynamics, nucleation-promoting factors, cryo-EM structure
MeSH terms
Actins, Animals, Humans, Actin Cytoskeleton, Models, Molecular, Protein Binding, Cryoelectron Microscopy, Cortactin, Actin-Related Protein 2-3 Complex, Actin-Related Protein 3

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