Yadav Sharda Prasad, Sharma Neel Kamal, Liu Chunqiao, Dong Lijin, Li Tiansen, Swaroop Anand
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Development. 2016 May 1;143(9):1491-501. doi: 10.1242/dev.130120. Epub 2016 Mar 10.
Defects in cilia centrosomal genes cause pleiotropic clinical phenotypes, collectively called ciliopathies. Cilia biogenesis is initiated by the interaction of positive and negative regulators. Centriolar coiled coil protein 110 (CP110) caps the distal end of the mother centriole and is known to act as a suppressor to control the timing of ciliogenesis. Here, we demonstrate that CP110 promotes cilia formation in vivo, in contrast to findings in cultured cells. Cp110(-/-) mice die shortly after birth owing to organogenesis defects as in ciliopathies. Shh signaling is impaired in null embryos and primary cilia are reduced in multiple tissues. We show that CP110 is required for anchoring of basal bodies to the membrane during cilia formation. CP110 loss resulted in an abnormal distribution of core components of subdistal appendages (SDAs) and of recycling endosomes, which may be associated with premature extension of axonemal microtubules. Our data implicate CP110 in SDA assembly and ciliary vesicle docking, two requisite early steps in cilia formation. We suggest that CP110 has unique context-dependent functions, acting as both a suppressor and a promoter of ciliogenesis.
纤毛中心体基因的缺陷会导致多效性临床表型，统称为纤毛病。纤毛的生物发生由正负调节因子的相互作用启动。中心粒卷曲螺旋蛋白110（CP110）覆盖母中心粒的远端，已知其作为一种抑制因子来控制纤毛发生的时间。在此，我们证明，与在培养细胞中的发现相反，CP110在体内促进纤毛形成。Cp110基因敲除小鼠出生后不久因器官发生缺陷而死亡，就像在纤毛病中一样。在缺失胚胎中Shh信号受损，多个组织中的初级纤毛减少。我们表明，CP110是纤毛形成过程中基体锚定到膜所必需的。CP110的缺失导致亚远端附属物（SDA）和回收内体的核心成分分布异常，这可能与轴丝微管的过早延伸有关。我们的数据表明CP110参与SDA组装和纤毛小泡对接，这是纤毛形成过程中两个必要的早期步骤。我们认为CP110具有独特的上下文依赖性功能，既是纤毛发生的抑制因子又是促进因子。
