Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation
doi: 10.1038/ncb2274
pmid: 21685893
Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation
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.
- RIKEN Japan
- RIKEN Center for Biosystems Dynamics Research Japan
Cell Cycle Proteins, Epithelial Cells, Nerve Tissue Proteins, Rats, Isoenzymes, Cytoskeletal Proteins, Mice, Dogs, HEK293 Cells, Intercellular Junctions, Mutation, Animals, Humans, RNA Interference, Phosphorylation, Carrier Proteins, Cell Adhesion Molecules, Cell Shape, Protein Kinase C, Adaptor Proteins, Signal Transducing
Cell Cycle Proteins, Epithelial Cells, Nerve Tissue Proteins, Rats, Isoenzymes, Cytoskeletal Proteins, Mice, Dogs, HEK293 Cells, Intercellular Junctions, Mutation, Animals, Humans, RNA Interference, Phosphorylation, Carrier Proteins, Cell Adhesion Molecules, Cell Shape, Protein Kinase C, Adaptor Proteins, Signal Transducing
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