Singh, S. P. , Thomason, P. A. and Insall, R. H. (2021) Extracellular signalling modulates Scar/WAVE complex activity through Abi phosphorylation. Cells, 10(12), 3485. (doi: 10.3390/cells10123485) (PMID:34943993) (PMCID:PMC8700165)
Text
260556.pdf - Published Version Available under License Creative Commons Attribution. 8MB |
Abstract
The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here, we report that the Abi subunit—but not Scar—is phosphorylated in response to extracellular signalling in Dictyostelium cells. Like Scar, Abi is phosphorylated after the complex has been activated, implying that Abi phosphorylation modulates pseudopodia, rather than causing new ones to be made. Consistent with this, Scar complex mutants that cannot bind Rac are also not phosphorylated. Several environmental cues also affect Abi phosphorylation—cell-substrate adhesion promotes it and increased extracellular osmolarity diminishes it. Both unphosphorylatable and phosphomimetic Abi efficiently rescue the chemotaxis of Abi KO cells and pseudopodia formation, confirming that Abi phosphorylation is not required for activation or inactivation of the Scar/WAVE complex. However, pseudopodia and Scar patches in the cells with unphosphorylatable Abi protrude for longer, altering pseudopod dynamics and cell speed. Dictyostelium, in which Scar and Abi are both unphosphorylatable, can still form pseudopods, but migrate substantially faster. We conclude that extracellular signals and environmental responses modulate cell migration by tuning the behaviour of the Scar/WAVE complex after it has been activated.
Item Type: | Articles |
---|---|
Additional Information: | This work was supported by Cancer Research UK core grant numbers A17196 and Multidisciplinary Award A20017 and EPSRC grant EP/S030875/1 to R.H.I. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Thomason, Dr Peter and Singh, Dr Shashi and Insall, Professor Robert |
Creator Roles: | Singh, S. P.Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Visualization Thomason, P. A.Methodology, Resources, Writing – review and editing Insall, R. H.Conceptualization, Formal analysis, Writing – review and editing, Visualization, Supervision, Project administration, Funding acquisition |
Authors: | Singh, S. P., Thomason, P. A., and Insall, R. H. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Cells |
Publisher: | MDPI |
ISSN: | 2073-4409 |
ISSN (Online): | 2073-4409 |
Published Online: | 10 December 2021 |
Copyright Holders: | Copyright © 2021 The Authors |
First Published: | First published in Cells 10(12): 3485 |
Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record