Hancock, L.P., Palmer, J.S., Allwood, E.G. et al. (5 more authors) (2025) Competitive binding of actin and SH3 domains at proline-rich regions of Las17/WASP regulates actin polymerisation. Communications Biology, 8 (1). 759. ISSN 2399-3642
Abstract
Eukaryotic actin filaments bind factors that regulate their assembly and disassembly creating a self-organising system, the actin cytoskeleton. Despite extensive knowledge of signals that modulate actin organisation, significant gaps remain in our understanding of spatiotemporal regulation of de novo filament initiation. Yeast Las17/WASP is essential for actin polymerisation initiation supporting membrane invagination in Saccharomyces cerevisiae endocytosis and therefore its tight regulation is critical. The adaptor protein Sla1 inhibits Las17 but mechanisms underpinning Las17 activation remain elusive. Here we show that Las17 binding of tandem Sla1 SH3 domains is >100-fold stronger than single domains. Furthermore, SH3 domains directly compete with G-actin for binding in the Las17 polyproline region, thus rationalising how SH3 interactions can affect actin polymerisation despite their distance from C-terminal actin-binding and Arp2/3-interacting VCA domains. Our data and proposed model also highlight the likely importance of multiple weak interactions that together ensure spatial and temporal regulation of endocytosis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Actin; Cytoskeletal proteins |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 May 2025 14:36 |
Last Modified: | 19 May 2025 14:36 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s42003-025-08188-4 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:226841 |