Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8TEW0 (Par3)
 364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. 2168 93

Willin is a FERM-domain protein, which is related to the Drosophila Expanded, a protein known to be a component of the Hippo signaling pathway. We recently showed that Willin localizes at the apical junctional complex (AJC) in epithelial cells together with Par3 and regulates the contractility of the circumferential actomyosin cables by recruiting aPKC to the AJC. However, it remains unresolved how Willin becomes associated with the AJC. Here, we report that Willin binds to nectins, Ig-family proteins, which also localize at the AJC via their homophilic or heterophilic interactions, and this binding participates in the junctional recruitment of Willin. In addition, we report that the positioning of nectins at the AJC is dependent on their binding to afadin. Thus, our results suggest that the nectin-afadin interaction plays a role in the correct localization of Willin.
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PMID:Nectins localize Willin to cell-cell junctions. 2251 38