Extracellular signalling modulates Scar/WAVE complex activity through Abi phosphorylation

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)

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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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303232EPSRC Centre for Multiscale soft tissue mechanics with MIT and POLIMI (SofTMech-MP)Xiaoyu LuoEngineering and Physical Sciences Research Council (EPSRC)EP/S030875/1M&S - Mathematics