Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis

Qingwen Xu, Yuxia Zhang, Qing Wei, Yan Huang, Jinghua Hu, Kun Ling

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 Iγ phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIγ) and inositol polyphosphate-5-phosphatase E (INPP5E), a Joubert syndrome protein, localize to the centrosome and coordinate the initiation of ciliogenesis. PIPKIγ 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 PIPKIγ and INPP5E at the centrosome/ciliary base, is vital for ciliogenesis by regulating the CEP164-dependent recruitment of TTBK2.

Original languageEnglish (US)
Article number10777
JournalNature Communications
Volume7
DOIs
StatePublished - Feb 26 2016

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inositols
Phosphatidylinositol Phosphates
Polyphosphates
phosphatases
Phosphoric Monoester Hydrolases
Inositol
phosphates
Phosphotransferases
Centrosome
Basal Bodies
proteins
appendages
homeostasis
Axoneme
Microtubule Proteins
Inborn Genetic Diseases
Proteins
Cilia
elongation
Medical Genetics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis. / Xu, Qingwen; Zhang, Yuxia; Wei, Qing; Huang, Yan; Hu, Jinghua; Ling, Kun.

In: Nature Communications, Vol. 7, 10777, 26.02.2016.

Research output: Contribution to journalArticle

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AU - Ling, Kun

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