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

Current Biology : CB
Sabrya C CarimMartin Lowe

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)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.

Citations

May 24, 2019·The Journal of Cell Biology·Virginie E MondinSébastien Carréno
Feb 9, 2020·Nature Reviews. Molecular Cell Biology·Jeremy G CarltonUlrike S Eggert
Jun 22, 2021·Journal of Cell Science·Nicholas V G Iannantuono, Gregory Emery
Oct 22, 2021·Human Molecular Genetics·Francesca OltrabellaMartin Lowe

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Methods Mentioned

BETA
Pull-down
Confocal microscopy
fluorescence microscopy
dIPIP
Fluorescence
PCR
transfections
transfection
FACS
in vitro transcription

Key Resources (RRID) Mentioned

CVCL_0030
Addgene_58470

Software Mentioned

Volocity
GraphPad
ImageJ
GraphPad Prism
Adobe illustrator
Image Pro
Huygens Volume Imaging
Flexitube Genesolution
FIJI
MetaMorph

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