Department of Biology, Eberly College of Science, The Pennsylvania State University, University Park, PA 16802.
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2164-9. doi: 10.1073/pnas.1318737111. Epub 2014 Jan 27.
The primary cilium plays critical roles in vertebrate development and physiology, but the mechanisms underlying its biogenesis remain poorly understood. We investigated the molecular function of C2 calcium-dependent domain containing 3 (C2cd3), an essential regulator of primary cilium biogenesis. We show that C2cd3 is localized to the centriolar satellites in a microtubule- and Pcm1-dependent manner; however, C2cd3 is dispensable for centriolar satellite integrity. C2cd3 is also localized to the distal ends of both mother and daughter centrioles and is required for the recruitment of five centriolar distal appendage proteins: Sclt1, Ccdc41, Cep89, Fbf1, and Cep164. Furthermore, loss of C2cd3 results in failure in the recruitment of Ttbk2 to the ciliary basal body as well as the removal of Cp110 from the ciliary basal body, two critical steps in initiating ciliogenesis. C2cd3 is also required for recruiting the intraflagellar transport proteins Ift88 and Ift52 to the mother centriole. Consistent with a role in distal appendage assembly, C2cd3 is essential for ciliary vesicle docking to the mother centriole. Our results suggest that C2cd3 regulates cilium biogenesis by promoting the assembly of centriolar distal appendages critical for docking ciliary vesicles and recruiting other essential ciliogenic proteins.
初级纤毛在脊椎动物发育和生理学中起着关键作用，但初级纤毛发生的机制仍知之甚少。我们研究了 C2 钙依赖性结构域包含 3 号（C2cd3）的分子功能，C2cd3 是初级纤毛发生的必需调节因子。我们发现 C2cd3 以微管和 Pcm1 依赖的方式定位于中心粒卫星；然而，C2cd3 对于中心粒卫星的完整性不是必需的。C2cd3 还定位于母和子中心粒的远端，并招募五个中心粒远端附属蛋白：Sclt1、Ccdc41、Cep89、Fbf1 和 Cep164。此外，C2cd3 的缺失导致 Ttbk2 不能募集到纤毛基体，以及 Cp110 从纤毛基体中去除，这是启动纤毛发生的两个关键步骤。C2cd3 还需要招募内鞭毛运输蛋白 Ift88 和 Ift52 到母中心粒。与在远端附属物组装中的作用一致，C2cd3 对于将纤毛小泡停泊到母中心粒是必需的。我们的结果表明，C2cd3 通过促进对停靠纤毛小泡和招募其他必需的纤毛发生蛋白至关重要的中心粒远端附属物的组装来调节纤毛发生。
