Department of Biological Sciences, National Creative Research Initiatives Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
Department of Biology, Chungnam National University, Daejeon 305-764, Korea.
Nat Commun. 2014 Nov 4;5:5370. doi: 10.1038/ncomms6370.
Primary cilia are microtubule-based organelles that protrude from polarized epithelial cells. Although many structural and trafficking molecules that regulate ciliogenesis have been discovered, signalling proteins are not well defined. Here we show that the MST1/2-SAV1 complex, a core component of the Hippo pathway, promotes ciliogenesis. MST1 is activated during ciliogenesis and localizes to the basal body of cilia. Depletion of MST1/2 or SAV1 impairs ciliogenesis in cultured cells and induces ciliopathy phenotypes in zebrafish. MST1/2-SAV1 regulates ciliogenesis through two independent mechanisms: MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex; and MST1/2-SAV1 associates with the NPHP transition-zone complex, promoting ciliary localization of multiple ciliary cargoes. Our results suggest that components of the Hippo pathway contribute to establish a polarized cell structure in addition to regulating proliferation.
初级纤毛是从极化上皮细胞中伸出的微管基细胞器。虽然已经发现了许多调节纤毛发生的结构和运输分子，但信号蛋白的定义还不明确。在这里，我们表明 MST1/2-SAV1 复合物，Hippo 通路的核心组成部分，促进纤毛发生。MST1 在纤毛发生过程中被激活，并定位于纤毛的基体。MST1/2 或 SAV1 的耗竭会损害培养细胞中的纤毛发生，并在斑马鱼中诱导纤毛病表型。MST1/2-SAV1 通过两种独立的机制调节纤毛发生：MST1/2 结合并磷酸化 Aurora 激酶 A（AURKA），导致 AURKA/HDAC6 纤毛解体复合物解离；MST1/2-SAV1 与 NPHP 过渡区复合物结合，促进多个纤毛货物的纤毛定位。我们的结果表明，Hippo 通路的组成部分除了调节增殖外，还有助于建立极化细胞结构。
