Walentek Peter, Quigley Ian K, Sun Dingyuan I, Sajjan Umeet K, Kintner Christopher, Harland Richard M
Division of Genetics, Genomics and Development, Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
Elife. 2016 Sep 13;5:e17557. doi: 10.7554/eLife.17557.
Upon cell cycle exit, centriole-to-basal body transition facilitates cilia formation. The centriolar protein Cp110 is a regulator of this process and cilia inhibitor, but its positive roles in ciliogenesis remain poorly understood. Using we show that Cp110 inhibits cilia formation at high levels, while optimal levels promote ciliogenesis. Cp110 localizes to cilia-forming basal bodies and rootlets, and is required for ciliary adhesion complexes that facilitate Actin interactions. The opposing roles of Cp110 in ciliation are generated in part by coiled-coil domains that mediate preferential binding to centrioles over rootlets. Because of its dual role in ciliogenesis, Cp110 levels must be precisely controlled. In multiciliated cells, this is achieved by both transcriptional and post-transcriptional regulation through ciliary transcription factors and microRNAs, which activate and repress to produce optimal Cp110 levels during ciliogenesis. Our data provide novel insights into how Cp110 and its regulation contribute to development and cell function.
细胞周期退出时,中心粒向基体的转变促进纤毛形成。中心粒蛋白Cp110是这一过程的调节因子和纤毛抑制剂,但其在纤毛发生中的积极作用仍知之甚少。我们的研究表明,高水平的Cp110会抑制纤毛形成,而最佳水平则会促进纤毛发生。Cp110定位于形成纤毛的基体和小根,是促进肌动蛋白相互作用的纤毛粘附复合物所必需的。Cp110在纤毛形成中的相反作用部分是由卷曲螺旋结构域产生的,该结构域介导其优先与中心粒而非小根结合。由于Cp110在纤毛发生中具有双重作用,其水平必须得到精确控制。在多纤毛细胞中,这是通过纤毛转录因子和微小RNA的转录和转录后调控来实现的,它们在纤毛发生过程中激活和抑制,以产生最佳的Cp110水平。我们的数据为Cp110及其调控如何影响发育和细胞功能提供了新的见解。