IPIP27 coordinates PtdIns(4,5)P2 homeostasis for successful cytokinesis

Sabrya C. Carim, Khaled Ben El Kadhi, Guanhua Yan, Sean Sweeney, Gilles R. Hickson, Sebastien Carreno, Martin Lowe

Research output: Contribution to journalArticlepeer-review

Abstract

During cytokinesis, an actomyosin contractile ring drives the separation of the two daughter cells. A key molecule in this process is the inositol lipid PtdIns(4,5)P 2 , which recruits numerous factors to the equatorial region for contractile ring assembly. Despite the importance of PtdIns(4,5)P 2 in cytokinesis, the regulation of this lipid in cell division remains poorly understood. Here, we identify a role for IPIP27 in mediating cellular PtdIns(4,5)P 2 homeostasis. IPIP27 scaffolds the inositol phosphatase oculocerebrorenal syndrome of Lowe (OCRL) by coupling it to endocytic BAR domain proteins. Loss of IPIP27 causes accumulation of PtdIns(4,5)P 2 on aberrant endomembrane vacuoles, mislocalization of the cytokinetic machinery, and extensive cortical membrane blebbing. This phenotype is observed in Drosophila and human cells and can result in cytokinesis failure. We have therefore identified IPIP27 as a key modulator of cellular PtdIns(4,5)P 2 homeostasis required for normal cytokinesis. The results indicate that scaffolding of inositol phosphatase activity is critical for maintaining PtdIns(4,5)P 2 homeostasis and highlight a critical role for this process in cell division. Carim et al. reveal that the IPIP27 protein, which physically couples the inositol phosphatase OCRL to endocytic BAR domain proteins, is required for cellular phosphoinositide homeostasis and normal cell division. The results show the importance of physically scaffolding inositol phosphatase activity within cells.

Original languageEnglish
Pages (from-to)775-789
Number of pages15
JournalCurrent Biology
Volume29
Issue number5
Early online date21 Feb 2019
DOIs
Publication statusPublished - 4 Mar 2019

Bibliographical note

Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Keywords

  • BAR domain protein
  • IPIP27
  • OCRL
  • PtdIns(4,5)P
  • SH3PX1
  • actin
  • cytokinesis
  • endosome
  • phosphoinositide

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