Atypical Protein Kinase C Promotes its own Asymmetric Localisation by Phosphorylating Cdc42 in Polarising Cells

Abstract

SUMMARYAtypical protein kinase C (aPKC) is a major regulator of cell polarity. Acting in conjunction with Par6, Par3 and the small GTPase Cdc42, aPKC becomes asymmetrically localised and drives the polarisation of cells. aPKC activity is crucial for its own asymmetric localisation, suggesting a hitherto unknown feedback mechanism contributing to polarisation. Here we show inC. eleganszygotes that the feedback relies on CDC-42 phosphorylation at serine 71 by aPKC, which in turn results in aPKC dissociation from CDC-42. The dissociated aPKC then associates with PAR-3 clusters, which are transported anteriorly by actomyosin-based cortical flow. Moreover, the turnover of aPKC-mediated CDC-42 phosphorylation regulates the organisation of the actomyosin cortex that drives aPKC asymmetry. Given the widespread role of aPKC and Cdc42 in cell polarity, this form of self-regulation of aPKC may be vital for the robust polarisation of many cell types.Key findings/graphical abstract–aPKC-mediated phosphorylation of CDC-42 on serine 71 dissociates aPKC from CDC-42–Dissociation of aPKC from CDC-42 promotes the anterior membrane localisation of aPKC with PAR-3–CDC-42 phosphorylation prevents the anterior membrane enrichment of CDC-42–Phosphorylated CDC-42 is enriched at actomyosin foci and induces their disorganisation