INPP5E preserves genomic Stability through regulation of mitosis

Elizabeth A. Sierra Potchanant, Donna Cerabona, Zahi Abdul Sater, Ying He, Zejin Sun, Jeff Gehlhausen, Grzegorz Nalepa

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development.

Original languageEnglish (US)
Article numbere00500-16
JournalMolecular and cellular biology
Volume37
Issue number6
DOIs
StatePublished - 2017

Keywords

  • Aneuploidy
  • Cell cycle
  • Centrosomes
  • INPP5E
  • Mitosis
  • Spindle assembly checkpoint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sierra Potchanant, E. A., Cerabona, D., Sater, Z. A., He, Y., Sun, Z., Gehlhausen, J., & Nalepa, G. (2017). INPP5E preserves genomic Stability through regulation of mitosis. Molecular and cellular biology, 37(6), [e00500-16]. https://doi.org/10.1128/MCB.00500-16