| First Author | Xu Q | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10777 | PubMed ID | 26916822 |
| Mgi Jnum | J:234830 | Mgi Id | MGI:5790925 |
| Doi | 10.1038/ncomms10777 | Citation | Xu Q, et al. (2016) Phosphatidylinositol phosphate kinase PIPKIgamma and phosphatase INPP5E coordinate initiation of ciliogenesis. Nat Commun 7:10777 |
| abstractText | 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 Igamma phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIgamma) and inositol polyphosphate-5-phosphatase E (INPP5E), a Joubert syndrome protein, localize to the centrosome and coordinate the initiation of ciliogenesis. PIPKIgamma 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 PIPKIgamma and INPP5E at the centrosome/ciliary base, is vital for ciliogenesis by regulating the CEP164-dependent recruitment of TTBK2. |
