Centre for Organismal Studies (COS), University of Heidelberg, 69120 Heidelberg, Germany.
German Cancer Research Centre (DKFZ), DKFZ-ZMBH Alliance, Molecular Biology of Centrosomes and Cilia Group, 69120 Heidelberg, Germany.
J Cell Sci. 2018 Sep 20;131(18):jcs223594. doi: 10.1242/jcs.223594.
Cilia perform essential signalling functions during development and tissue homeostasis. A key event in ciliogenesis occurs when the distal appendages of the mother centriole form a platform that docks ciliary vesicles and removes CP110-Cep97 inhibitory complexes. Here, we analysed the role of LRRC45 in appendage formation and ciliogenesis. We show that the core appendage proteins Cep83 and SCLT1 recruit LRRC45 to the mother centriole. Once there, LRRC45 recruits the keratin-binding protein FBF1. The association of LRRC45 with the basal body of primary and motile cilia in both differentiated and stem cells reveals a broad function in ciliogenesis. In contrast to the appendage components Cep164 and Cep123, LRRC45 was not essential for either docking of early ciliary vesicles or for removal of CP110. Rather, LRRC45 promotes cilia biogenesis in CP110-uncapped centrioles by organising centriolar satellites, establishing the transition zone and promoting the docking of Rab8 GTPase-positive vesicles. We propose that, instead of acting solely as a platform to recruit early vesicles, centriole appendages form discrete scaffolds of cooperating proteins that execute specific functions that promote the initial steps of ciliogenesis.
纤毛在发育和组织稳态中发挥重要的信号作用。中心粒远端附属物形成一个平台，停靠纤毛囊泡并去除 CP110-Cep97 抑制复合物，这是纤毛发生过程中的一个关键事件。在这里，我们分析了 LRRC45 在附属物形成和纤毛发生中的作用。我们表明，核心附属蛋白 Cep83 和 SCLT1 将 LRRC45 招募到母中心粒。一旦到达那里，LRRC45 就会招募角蛋白结合蛋白 FBF1。LRRC45 在分化细胞和干细胞中的初级和运动纤毛的基底体外周与基底体的关联揭示了其在纤毛发生中的广泛功能。与附属物成分 Cep164 和 Cep123 不同，LRRC45 对于早期纤毛囊泡的停靠或 CP110 的去除都不是必需的。相反，LRRC45 通过组织中心粒卫星、建立过渡区和促进 Rab8 GTP 酶阳性囊泡的停靠，促进 CP110 无帽中心粒的纤毛发生。我们提出，中心粒附属物不是作为招募早期囊泡的唯一平台，而是形成具有特定功能的离散合作蛋白支架，这些支架可以促进纤毛发生的初始步骤。
