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Pak1 kinase maintains apical membrane identity in epithelia
journal contributionposted on 2020-10-28, 14:59 authored by Mario Aguilar Aragon, Ahmed Elbediwy, Valentina Foglizzo, Georgina C Fletcher, Vivian SW Li, Barry J Thompson
Epithelial cells are polarized along their apical-basal axis by the action of the small GTPase Cdc42, which is known to activate the aPKC kinase at the apical domain. However, loss of aPKC kinase activity was reported to have only mild effects on epithelial cell polarity. Here, we show that Cdc42 also activates a second kinase, Pak1, to specify apical domain identity in Drosophila and mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1 kinase leads to a complete loss of epithelial polarity and morphology, with cells losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1. This function of Pak1 downstream of Cdc42 is distinct from its role in regulating integrins or E-cadherin. Our results define a conserved dual-kinase mechanism for the control of apical membrane identity in epithelia.
Cdc42DrosophilaPak1ZO-1aPKCapical domainepithelial polarityorganoidsAmino Acid SequenceAnimalsCaco-2 CellsCell MembraneCell PolarityDrosophila ProteinsDrosophila melanogasterEpithelial CellsHumansMicePhosphorylationProtein Kinase CRNA Interferencep21-Activated KinasesThompson FC001180PC-ackLi, V FC0011050601 Biochemistry and Cell Biology