CRB2 controls primary ciliogenesis in association with PAR6α, HOOK2 and RAB8A

Abstract

Ciliogenesis is an essential process in animal development and physiology and when affected, the origin of severe pathologies called ciliopathies. CRB2 has been recently implicated when mutated in several pathologies such as retina degeneration and a ciliopathylike syndrome. Here, we have investigated the role of CRB2 in primary ciliogenesis and showed that CRB2 depletion blocks the formation of the ciliary vesicle after activation of the mother centriole, indicating a defect in either transport or anchoring of the ciliary vesicle.CRB2 is accumulated in intracellular vesicles in the vicinity of the centrosome and we showed here that CRB2 forms a complex made of HOOK2 and PAR6a, two proteins important for primary ciliogenesis or centrosome integrity. In addition, CRB2 interacts with RAB8A which over-expression rescued CRB2 knockdown. All together, these findings indicate that CRB2 regulates a membrane transport step essential for the formation of the ciliary vesicle.

Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina

“…CRB2 -linked pathology has been debated as a ciliopathy-like syndrome as the pathological defects are comparable to those described in ciliopathy patients ( 70 ). CRB2 has been among others detected in vesicles near the centrosome in ARPE19 cells and has been shown to be required for primary ciliary vesicle formation and anchoring ( 74 Preprint ). In zebrafish, Crb2 is required for the elongation of the photoreceptor inner segment and of the primary cilium of kidney cells ( 35 , 75 ).…”