Centrosomal protein CP110 controls maturation of mother centriole during cilia biogenesis

Abstract

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.

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis

“…CP110 is a key marker in ciliogenesis process (25,26). Our previous study demonstrated that the increased expression of CP110 in mucosa from patients with chronic rhino sinusitis (CRS) was associated to the poor ciliation (15).…”

Primary Cilia and Mammalian Hedgehog Signaling

“…Tau tubulin kinase 2 (TTBK2) is required for cilia initiation and mutants lack all cilia and Hh-dependent ventral neural cell types (Goetz et al 2012). Embryos that lack CP110, a protein that localizes to the distal ends of mother centrioles, also have fewer cilia and mild defects in Hh signaling (Yadav et al, 2016). …”

Open Sesame: How Transition Fibers and the Transition Zone Control Ciliary Composition

“…Expansion of this ciliary vesicle gives rise to the ciliary membrane, which is assembled in parallel with the axoneme. Axoneme outgrowth is associated with removal from the distal mother centriole of CP110, a protein with both positive and negative roles in early ciliogenesis (Spektor et al 2007; Tsang et al 2008; Kobayashi et al 2011; Yadav et al 2016). Axoneme formation also involves the construction of the TZ and recruitment of intraflagellar transport (IFT) particles, the microtubule motor-driven complexes that mediate ciliary transport and assembly (Lu et al 2015).…”