Multi-monoubiquitylation controls VASP-mediated actin dynamics.

Autor:	McCormick LE; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Suarez C; Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA., Herring LE; Michael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Cannon KS; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Kovar DR; Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA., Brown NG; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Gupton SL; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2024 Jan 15; Vol. 137 (2). Date of Electronic Publication: 2024 Jan 26.
DOI:	10.1242/jcs.261527
Abstrakt:	The actin cytoskeleton performs multiple cellular functions, and as such, actin polymerization must be tightly regulated. We previously demonstrated that reversible, non-degradative ubiquitylation regulates the function of the actin polymerase VASP in developing neurons. However, the underlying mechanism of how ubiquitylation impacts VASP activity was unknown. Here, we show that mimicking multi-monoubiquitylation of VASP at K240 and K286 negatively regulates VASP interactions with actin. Using in vitro biochemical assays, we demonstrate the reduced ability of multi-monoubiquitylated VASP to bind, bundle, and elongate actin filaments. However, multi-monoubiquitylated VASP maintained the ability to bind and protect barbed ends from capping protein. Finally, we demonstrate the electroporation of recombinant multi-monoubiquitylated VASP protein altered cell spreading morphology. Collectively, these results suggest a mechanism in which ubiquitylation controls VASP-mediated actin dynamics. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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