Tsang William Y, Bossard Carine, Khanna Hemant, Peränen Johan, Swaroop Anand, Malhotra Vivek, Dynlacht Brian David
Department of Pathology and Cancer Institute, New York University School of Medicine, 522 1(st) Avenue, New York, NY 10016, USA.
Dev Cell. 2008 Aug;15(2):187-97. doi: 10.1016/j.devcel.2008.07.004.
Primary cilia are nonmotile organelles implicated in signaling and sensory functions. Understanding how primary cilia assemble could shed light on the many human diseases caused by mutations in ciliary proteins. The centrosomal protein CP110 is known to suppress ciliogenesis through an unknown mechanism. Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease--in a discrete complex separable from other CP110 complexes involved in regulating the centrosome cycle. Ablation of CEP290 prevents ciliogenesis without affecting centrosome function or cell-cycle progression. Interaction with CEP290 is absolutely required for the ability of CP110 to suppress primary cilia formation. Furthermore, CEP290 and CP110 interact with Rab8a, a small GTPase required for cilia assembly. Depletion of CEP290 interferes with localization of Rab8a to centrosomes and cilia. Our results suggest that CEP290 cooperates with Rab8a to promote ciliogenesis and that this function is antagonized by CP110.
初级纤毛是参与信号传导和感觉功能的非运动性细胞器。了解初级纤毛如何组装可能有助于揭示由纤毛蛋白突变引起的许多人类疾病。已知中心体蛋白CP110通过未知机制抑制纤毛发生。在此，我们报告CP110与CEP290（一种其缺陷与人类纤毛疾病有关的蛋白质）在一个离散复合物中相互作用，该复合物可与参与调节中心体周期的其他CP110复合物分离。CEP290的缺失可阻止纤毛发生，而不影响中心体功能或细胞周期进程。CP110抑制初级纤毛形成的能力绝对需要与CEP290相互作用。此外，CEP290和CP110与Rab8a相互作用，Rab8a是纤毛组装所需的一种小GTP酶。CEP290的缺失会干扰Rab8a定位于中心体和纤毛。我们的结果表明，CEP290与Rab8a协同促进纤毛发生，并且该功能受到CP110的拮抗。
