RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
Nat Cell Biol. 2011 Jun 19;13(7):860-6. doi: 10.1038/ncb2274.
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.
顶端域收缩对于调节上皮形态发生很重要。上皮细胞通过顶端连接复合体（AJC）连接，AJC 上排列着环形的肌动球蛋白缆索。这些缆索的收缩性受 Rho 相关激酶（ROCK）调节。在这里，我们报告说，Willin（一种 FERM 结构域蛋白）和 Par3（一种极性调节蛋白）协同调节 ROCK 依赖性顶端收缩。我们发现，Willin 独立于 Par3 将 aPKC 和 Par6 募集到 AJC。Willin 和 Par3 的同时耗竭完全将 aPKC 和 Par6 从 AJC 中去除，并诱导顶端收缩。诱导的收缩是通过 AJC 相关 ROCK 水平的上调引起的，这是由于 aPKC 的缺失。我们的结果表明，aPKC 使 ROCK 磷酸化并抑制其连接定位，从而使细胞能够保持正常形状的顶端区域。因此，我们发现了一个 Willin/Par3-aPKC-ROCK 通路，它控制着上皮的顶端形态。
