Mechanisms of cell cycle-dependent conversion of the mother centriole to the basal body

初级纤毛是由中心粒母体转化为基体而形成的。睫状体膜是由囊泡融合到核周围体而产生的，这一过程需要Rab 11介导的Rabin 8的募集、Rab 8的激活和Rabin 8与Sec 15的结合，Sec 15是外囊的一个组成部分。这项研究表明，NDR 2在Ser-272磷酸化Rabin 8，这种磷酸化的缺陷损害了睫状体前膜的组装和纤毛发生，导致含有Rabin 8/Rab 11的囊泡在中心体周围积聚。Rabin 8与GTP结合的Rab 11和磷脂酰丝氨酸（PS）结合并共定位于粒周囊泡上。Rabin 8的磷酸模拟S272 E突变降低了对PS的亲和力，但增加了对Sec 15的亲和力。这些结果表明，NDR 2介导的Rabin 8磷酸化通过触发Rabin 8从PS到Sec 15的结合特异性的转换，从而促进Rab 8的局部激活和睫状膜形成，对纤毛发生至关重要。

Primary cilia are formed by conversion of the mother centriole to the basal body. Ciliary membranes are generated by fusion of vesicles to the pericentrosome, a process requiring Rab11-mediated recruitment of Rabin8, Rab8 activation and Rabin8 binding to Sec15, a component of the exocyst.This study showed that NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis, resulting in accumulation of Rabin8/Rab11-containing vesicles at the pericentrosome. Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles. The phospho-mimetic S272E mutation of Rabin8 decreases affinity for PS but increases affinity for Sec15. These results suggest that NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15, thereby promoting local activation of Rab8 and ciliary membrane formation.