Willin and Par3 cooperatively regulate epithelial apical constriction through a PKC-mediated ROCK phosphorylation
Willin and Par3 cooperatively regulate epithelial apical constriction through a PKC-mediated ROCK phosphorylation
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DOI：
10.1038/ncb2274
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发表时间：
2011-07-01
影响因子：
21.3
通讯作者：
Takeichi, Masatoshi
中科院分区：
文献类型：
--
作者：
Ishiuchi, Takashi;Takeichi, Masatoshi
顶端结构域收缩对于调节上皮形态发生是重要的。上皮细胞通过顶端连接复合体（AJCs）连接，所述顶端连接复合体（AJCs）衬有周向肌动球蛋白缆。Secables的收缩性由Rho相关激酶（ROCK）调节。在这里，我们报告说，Willin（一个FERM结构域蛋白）和Par 3（极性调节蛋白）合作调节ROCK依赖的顶端收缩。我们发现，Willin招募aPKC和Par 6的AJC，独立于Par 3。同时消耗Willin和Par 3完全从AJCs中去除aPKC和Par 6并诱导根尖收缩。诱导收缩是通过上调AJC相关ROCK的水平，这是由于aPKC的丢失。我们的研究结果表明，aPKC磷酸化ROCK，并抑制其连接定位，使细胞保留正常形状的顶端域。因此，我们已经发现了一个Willin/Par 3-aPKC-ROCK途径，控制上皮顶端形态。
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 the secables 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, there by allowing cells to retain normally shaped apical domains. Thus, we have uncovered a Willin/Par3-aPKC-ROCK pathway that controls epithelial apical morphology.