Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK pho

Abstract

Willin and Par3 synergistically recruit aPKC to cell junctions, thus promoting aPKC-mediated phosphorylation of ROCK. This event inhibits ROCK junctional localization and apical constriction to maintain epithelial cell morphology. Apical-domain constriction is important for regulating epithelial morphogenesis. Epithelial cells are connected by apical junctional complexes (AJCs) that are lined with circumferential actomyosin cables. The contractility of these cables is regulated by Rho-associated kinases (ROCKs). Here, we report that Willin (a FERM-domain protein) and Par3 (a polarity-regulating protein) cooperatively regulate ROCK-dependent apical constriction. We found that Willin recruits aPKC and Par6 to the AJCs, independently of Par3. Simultaneous depletion of Willin and Par3 completely removed aPKC and Par6 from the AJCs and induced apical constriction. Induced constriction was through upregulation of the level of AJC-associated ROCKs, which was due to loss of aPKC. Our results indicate that aPKC phosphorylates ROCK and suppresses its junctional localization, thereby allowing cells to retain normally shaped apical domains. Thus, we have uncovered a Willin/Par3–aPKC–ROCK pathway that controls epithelial apical morphology.

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Ishiuchi, T., Takeichi, M. Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nat Cell Biol 13, 860–866 (2011). https://doi.org/10.1038/ncb2274

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