Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis

Abstract

Defects in cilia-centrosomal genes cause pleiotropic clinical phenotypes, collectively called ciliopathies. Cilia biogenesis is initiated by interaction of positive and negative regulators. The centriolar coiled coil protein CP110 caps the distal end of mother centriole and is shown to act as a suppressor to control the timing of ciliogenesis. Here we demonstrate that CP110 promotes cilia formation in vivo unlike the findings in cultured cells. Cp110 − / − mice die shortly after birth because of 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 membrane during cilia formation. CP110 loss resulted in abnormal distribution of core components of sub-distal appendages (SDA) 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.