Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex
Open accessAbstract
The Arp2/3 complex, a stable assembly of two actin-related proteins (Arp2 and Arp3) with five other subunits, caps the pointed end of actin filaments and nucleates actin polymerization with low efficiency. WASp and Scar are two similar proteins that bind the p21 subunit of the Arp2/3 complex, but their effect on the nucleation activity of the complex was not known. We report that full-length, recombinant human Scar protein, as well as N-terminally truncated Scar proteins, enhance nucleation by the Arp2/3 complex. By themselves, these proteins either have no effect or inhibit actin polymerization. The actin monomer-binding W domain and the p21-binding A domain from the C terminus of Scar are both required to activate Arp2/3 complex. A proline-rich domain in the middle of Scar enhances the activity of the W and A domains. Preincubating Scar and Arp2/3 complex with actin filaments overcomes the initial lag in polymerization, suggesting that efficient nucleation by the Arp2/3 complex requires assembly on the side of a preexisting filament-a dendritic nucleation mechanism. The Arp2/3 complex with full-length Scar, Scar containing P, W, and A domains, or Scar containing W and A domains overcomes inhibition of nucleation by the actin monomer-binding protein profilin, giving active nucleation over a low background of spontaneous nucleation. These results show that Scar and, likely, related proteins, such as the Cdc42 targets WASp and N-WASp, are endogenous activators of actin polymer…
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Knockdown of Cyfip1 in BV2 microglial cells using two different siRNAs resulted in a ~40% loss of WAVE2 expression without affecting ABI3.
“Knockdown (KD) of Cyfip1 in the BV2 microglial cell line using two different siRNAs resulted in a ~40% loss of WAVE2 expression (Fig. 3 B and C, siRNA #1 P < 0.01, siRNA #2 P < 0.05), WAVE2 being the subunit that contains the VCA domain that is required to activate Arp2/3 complex activity (47), without affecting protein expression of the AD risk gene, ABI3.”
From Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1 (2026) · cites this paper as [47]
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- Authors
- Machesky, L. M., Mullins, R. D., Higgs, H. N., Kaiser, D. A., Blanchoin, L., May, R. C., Hall, M. E., & Pollard, T. D.
- Affiliations
- Salk Institute for Biological Studies (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-03-30
- Volume
- 96
- Issue
- 7
- Pages
- 3739-3744
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22364
- OpenAlex
- W2007586038
- Cited by
- 773
- References
- 0
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 16 · 2023: 19 · 2022: 29 · 2021: 18 · 2020: 16 · 2019: 21 · 2018: 23 · 2017: 17 · 2016: 19 · 2015: 21 · 2014: 18 · 2013: 28 · 2012: 22
- FWCI
- 23.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Institute of General Medical Sciences (R01GM026338, GM 26338)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- Arp2/3 complex, actin nucleation, actin polymerization, wasps, actin-related proteins, A domain, proline-rich region, profilin, actin monomer binding
- MeSH terms
- Acanthamoeba, Actins, Animals, Cytoskeletal Proteins, Humans, Kinetics, Models, Molecular, Protein Conformation, Proteins, Rabbits, Recombinant Proteins, Protozoan Proteins, Muscle, Skeletal, Macromolecular Substances, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2, Actin-Related Protein 3
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