Phosphatidylinositol phosphate kinase PIPKI? and phosphatase INPP5E coordinate initiation of ciliogenesis.

ABSTRACT: Defective primary cilia are causative to a wide spectrum of human genetic disorders, termed ciliopathies. Although the regulation of ciliogenesis is intensively studied, how it is initiated remains unclear. Here we show that type I? phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKI?) and inositol polyphosphate-5-phosphatase E (INPP5E), a Joubert syndrome protein, localize to the centrosome and coordinate the initiation of ciliogenesis. PIPKI? counteracts INPP5E in regulating tau-tubulin kinase-2 (TTBK2) recruitment to the basal body, which promotes the removal of microtubule capping protein CP110 and the subsequent axoneme elongation. Interestingly, INPP5E and its product--PtdIns(4)P--accumulate at the centrosome/basal body in non-ciliated, but not ciliated, cells. PtdIns(4)P binding to TTBK2 and the distal appendage protein CEP164 compromises the TTBK2-CEP164 interaction and inhibits the recruitment of TTBK2. Our results reveal that PtdIns(4)P homoeostasis, coordinated by PIPKI? and INPP5E at the centrosome/ciliary base, is vital for ciliogenesis by regulating the CEP164-dependent recruitment of TTBK2.

SUBMITTER: Xu Q 

PROVIDER: S-EPMC4773430 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature