AUTHOR=Singh Shashi Prakash , Paschke Peggy , Tweedy Luke , Insall Robert H. 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.965921

DOI=10.3389/fmolb.2022.965921

ISSN=2296-889X

ABSTRACT=<p>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 <italic>Dictyostelium</italic> PKB and SGK kinases (encoded by <italic>pkbA</italic> and <italic>pkgB</italic>) are dispensable for chemotaxis towards folate. However, both are involved in the regulation of pseudopod formation and thus cell motility. Cells lacking <italic>pkbA</italic> and <italic>pkgB</italic> showed a substantial drop in cell speed. Actin polymerization is perturbed in <italic>pkbA-</italic> and reduced in <italic>pkgB-</italic> and <italic>pkbA-/pkgB-</italic> mutants. The Scar/WAVE complex, key catalyst of pseudopod formation, is recruited normally to the fronts of all mutant cells (<italic>pkbA</italic>-, <italic>pkgB</italic>- and <italic>pkbA</italic>-/<italic>pkgB</italic>-), 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.</p>