IPIP27 Coordinates PtdIns(4,5)P2 Homeostasis for Successful Cytokinesis

Sabrya C Carim,Khaled Ben El Kadhi,Guanhua Yan,Sean T Sweeney,Gilles R Hickson,Sébastien Carréno,Martin Lowe

doi:10.1016/j.cub.2019.01.043

Abstract

SummaryDuring 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)P2, which recruits numerous factors to the equatorial region for contractile ring assembly. Despite the importance of PtdIns(4,5)P2 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)P2 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)P2 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)P2 homeostasis required for normal cytokinesis. The results indicate that scaffolding of inositol phosphatase activity is critical for maintaining PtdIns(4,5)P2 homeostasis and highlight a critical role for this process in cell division.

Highlights

Cytokinesis, the final step of cell division, is a fundamental process that is required for organismal development and tissue homeostasis
Localization experiments in Drosophila S2 cells indicated the presence of dIPIP on cytoplasmic puncta that likely correspond to endocytic compartments, where it colocalizes with Drosophila ortholog of OCRL (dOCRL)
Depletion of dIPIP Results in Cytokinesis Failure Given that depletion of dOCRL results in a penetrant cytokinesis defect [31], we explored whether loss of dIPIP may disrupt cytokinesis. dIPIP was depleted from S2 cells using doublestranded RNA (Figure 1D), and cytokinesis failure assessed by counting the degree of multi-nucleation

Summary

Introduction

Cytokinesis, the final step of cell division, is a fundamental process that is required for organismal development and tissue homeostasis. The primary driver of contractile ring assembly is RhoA, which becomes activated by the Ect Rho-GEF in the equatorial region of the plasma membrane [1,2,3, 6]. Another key player is the phosphoinositide lipid PtdIns(4,5)P2, which is enriched in the equatorial region [7,8,9]. PtdIns(4,5)P2 is a strong inducer of actin assembly [10], and within the equatorial region it promotes the recruitment of various factors including Ect and anillin [11, 12], as well as ezrin, radixin, and moesin (ERM) proteins that help link the actin cytoskeleton to the plasma membrane [13]. It is important that the synthesis and removal of PtdIns(4,5)P2 are tightly controlled to ensure effective cytokinesis [9]

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