PIPKIγ targets to the centrosome and restrains centriole duplication

Qingwen Xu, Yuxia Zhang, Xunhao Xiong, Yan Huang, Jeffery L. Salisbury, Jinghua Hu, Kun Ling

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Centriole biogenesis depends on the polo-like kinase (PLK4) and a small group of structural proteins. The spatiotemporal regulation of these proteins at pre-existing centrioles is essential to ensure that centriole duplication occurs once per cell cycle. Here, we report that phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C, hereafter referred to as PIPKIγ) plays an important role in centriole fidelity. PIPKIγ localized in a ring-like pattern in the intermediate pericentriolar materials around the proximal end of the centriole in G1, S and G2 phases, but not in M phase. This localization was dependent upon an association with centrosomal protein of 152 KDa (CEP152). Without detaining cells in S or M phase, the depletion of PIPKIγ led to centriole amplification in a manner that was dependent upon PLK4 and spindle assembly abnormal protein 6 homolog (SAS6). The expression of exogenous PIPKIγ reduced centriole amplification that occurred as a result of endogenous PIPKIγ depletion, hydroxyurea treatment or PLK4 overexpression, suggesting that PIPKIγ is likely to function at the PLK4 level to restrain centriole duplication. Importantly, we found that PIPKIγ bound to the cryptic polo-box domain of PLK4 and that this binding reduced the kinase activity of PLK4. Together, our findings suggest that PIPKIγ is a novel negative regulator of centriole duplication, which acts by modulating the homeostasis of PLK4 activity.

Original languageEnglish (US)
Pages (from-to)1293-1305
Number of pages13
JournalJournal of cell science
Volume127
Issue number6
DOIs
StatePublished - Mar 1 2014

Keywords

  • CEP152
  • CEP192
  • Centriole duplication
  • PLK4
  • Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

ASJC Scopus subject areas

  • Cell Biology

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