The Rho-family GEF FARP2 is activated by aPKCι to control tight junction formation and polarity.
journal contributionposted on 12.12.2019 by Ahmed Elbediwy, Yixiao Zhang, Mathias Cobbaut, Philippe Riou, Ray S Tan, Selene K Roberts, Chris Tynan, Roger George, Svend Kjaer, Marisa L Martin-Fernandez, Barry J Thompson, Neil Q McDonald, Peter J Parker
Any type of content formally published in an academic journal, usually following a peer-review process.
The elaboration of polarity is central to organismal development and to the maintenance of functional epithelia. Among the controls determining polarity are the PAR proteins, PAR6, aPKCι and PAR3, regulating both known and unknown effectors. Here, we identify FARP2 as a 'RIPR' motif-dependent partner and substrate of aPKCι that is required for efficient polarisation and junction formation. Binding is conferred by a FERM/FA domain-kinase domain interaction and detachment promoted by aPKCι-dependent phosphorylation. FARP2 is shown to promote GTP loading of Cdc42, which is consistent with it being involved in upstream regulation of the polarising PAR6-aPKCι complex. However, we show that aPKCι acts to promote the localised activity of FARP2 through phosphorylation. We conclude that this aPKCι-FARP2 complex formation acts as a positive feedback control to drive polarisation through aPKCι and other Cdc42 effectors.This article has an associated First Person interview with the first author of the paper.