Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis

Abstract Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different act...

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Autores principales:	J. J. Tyler, I. I. Smaczynska-de Rooij, L. Abugharsa, J. S. Palmer, L. P. Hancock, E. G. Allwood, K. R. Ayscough
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da0e863e541247d19898cda32b0978d0
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spelling	oai:doaj.org-article:da0e863e541247d19898cda32b0978d02021-12-02T14:29:03ZPhosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis10.1038/s41598-021-88826-z2045-2322https://doaj.org/article/da0e863e541247d19898cda32b0978d02021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88826-zhttps://doaj.org/toc/2045-2322Abstract Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different actin binding proteins including WASP family proteins which regulate the actin nucleating complex Arp2/3. In this study we reveal a phosphorylation site, Serine 554, within the WH2 domain of the yeast WASP homologue Las17. Both phosphorylation and a phospho-mimetic mutation reduce actin monomer binding affinity while an alanine mutation, generated to mimic the non-phosphorylated state, increases actin binding affinity. The effect of these mutations on the Las17-dependent process of endocytosis in vivo was analysed and leads us to propose that switching of Las17 phosphorylation states may allow progression through distinct phases of endocytosis from site assembly through to the final scission stage. While the study is focused on Las17, the sole WASP family protein in yeast, our results have broad implications for our understanding of how a key residue in this conserved motif can underpin the many different actin regulatory roles with which WH2 domains have been associated.J. J. TylerI. I. Smaczynska-de RooijL. AbugharsaJ. S. PalmerL. P. HancockE. G. AllwoodK. R. AyscoughNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. J. Tyler I. I. Smaczynska-de Rooij L. Abugharsa J. S. Palmer L. P. Hancock E. G. Allwood K. R. Ayscough Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
description	Abstract Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different actin binding proteins including WASP family proteins which regulate the actin nucleating complex Arp2/3. In this study we reveal a phosphorylation site, Serine 554, within the WH2 domain of the yeast WASP homologue Las17. Both phosphorylation and a phospho-mimetic mutation reduce actin monomer binding affinity while an alanine mutation, generated to mimic the non-phosphorylated state, increases actin binding affinity. The effect of these mutations on the Las17-dependent process of endocytosis in vivo was analysed and leads us to propose that switching of Las17 phosphorylation states may allow progression through distinct phases of endocytosis from site assembly through to the final scission stage. While the study is focused on Las17, the sole WASP family protein in yeast, our results have broad implications for our understanding of how a key residue in this conserved motif can underpin the many different actin regulatory roles with which WH2 domains have been associated.
format	article
author	J. J. Tyler I. I. Smaczynska-de Rooij L. Abugharsa J. S. Palmer L. P. Hancock E. G. Allwood K. R. Ayscough
author_facet	J. J. Tyler I. I. Smaczynska-de Rooij L. Abugharsa J. S. Palmer L. P. Hancock E. G. Allwood K. R. Ayscough
author_sort	J. J. Tyler
title	Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
title_short	Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
title_full	Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
title_fullStr	Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
title_full_unstemmed	Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis
title_sort	phosphorylation of the wh2 domain in yeast las17/wasp regulates g-actin binding and protein function during endocytosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da0e863e541247d19898cda32b0978d0
work_keys_str_mv	AT jjtyler phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT iismaczynskaderooij phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT labugharsa phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT jspalmer phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT lphancock phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT egallwood phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis AT krayscough phosphorylationofthewh2domaininyeastlas17waspregulatesgactinbindingandproteinfunctionduringendocytosis
_version_	1718391281250467840

Phosphorylation of the WH2 domain in yeast Las17/WASP regulates G-actin binding and protein function during endocytosis

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