AKT and SGK kinases regulate cell migration by altering Scar/WAVE complex activation and Arp2/3 complex recruitment

Singh, S. P. , Paschke, P., Tweedy, L. and Insall, R. H. (2022) AKT and SGK kinases regulate cell migration by altering Scar/WAVE complex activation and Arp2/3 complex recruitment. Frontiers in Molecular Biosciences, 9, 965921. (doi: 10.3389/fmolb.2022.965921) (PMID:36106016) (PMCID:PMC9466652)

Abstract

Cell polarity and cell migration both depend on pseudopodia and lamellipodia formation. These are regulated by coordinated signaling acting through G-protein coupled receptors and kinases such as PKB/AKT and SGK, as well as the actin cytoskeletal machinery. Here we show that both Dictyostelium PKB and SGK kinases (encoded by pkbA and pkgB) are dispensable for chemotaxis towards folate. However, both are involved in the regulation of pseudopod formation and thus cell motility. Cells lacking pkbA and pkgB showed a substantial drop in cell speed. Actin polymerization is perturbed in pkbA- and reduced in pkgB- and pkbA-/pkgB- mutants. The Scar/WAVE complex, key catalyst of pseudopod formation, is recruited normally to the fronts of all mutant cells (pkbA-, pkgB- and pkbA-/pkgB-), but is unexpectedly unable to recruit the Arp2/3 complex in cells lacking SGK. Consequently, loss of SGK causes a near-complete loss of normal actin pseudopodia, though this can be rescued by overexpression of PKB. Hence both PKB and SGK are required for correct assembly of F-actin and recruitment of the Arp2/3 complex by the Scar/WAVE complex during pseudopodia formation.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research United Kingdom core Grant Number A17196, A31287 and Multidisciplinary Award A20017 to RHI.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tweedy, Dr Luke and Insall, Professor Robert and Singh, Dr Shashi and Paschke, Dr Peggy

Creator Roles

Singh, S. P.: Conceptualization, Investigation, Methodology, Data curation, Formal analysis, Writing – original draft
Paschke, P.: Resources, Writing – review and editing
Tweedy, L.: Software, Writing – review and editing
Insall, R. H.: Supervision, Project administration, Funding acquisition, Writing – review and editing

• Authors: Singh, S. P., Paschke, P., Tweedy, L., 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: Frontiers in Molecular Biosciences
• Publisher: Frontiers Media
• ISSN: 2296-889X
• ISSN (Online): 2296-889X
• Copyright Holders: Copyright © 2022 Singh, Paschke, Tweedy and Insall
• First Published: First published in Frontiers in Molecular Biosciences 9: 965921
• Publisher Policy: Reproduced under a Creative Commons License