title: The inositol 5-phosphatase dOCRL controls PI(4,5)P2 homeostasis and is necessary for cytokinesis.
abstract: During cytokinesis, constriction of an equatorial actomyosin ring physically separates the two daughter cells. At the cleavage furrow, the phosphoinositide PI(4,5)P2 plays an important role by recruiting and regulating essential proteins of the cytokinesis machinery [1]. Accordingly, perturbation of PI(4,5)P2 regulation leads to abortive furrowing and binucleation [2-4]. To determine how PI(4,5)P2 is regulated during cytokinesis, we individually knocked down each of the enzymes controlling the phosphoinositide (PIP) cycle in Drosophila. We show that depletion of the Drosophila ortholog of human oculocerebrorenal syndrome of Lowe 1 (OCRL1), an inositol 5-phosphatase mutated in the X-linked disorder oculocerebrorenal Lowe syndrome, triggers a high rate of cytokinesis failure. In absence of dOCRL, several essential components of the cleavage furrow were found to be incorrectly localized on giant cytoplasmic vacuoles rich in PI(4,5)P2 and in endocytic markers. We demonstrate that dOCRL is associated with endosomes and that it dephosphorylates PI(4,5)P2 on internal membranes to restrict this phosphoinositide at the plasma membrane and thereby regulates cleavage furrow formation and ingression. Identification of dOCRL as essential for cell division may be important to understand the molecular basis of the phenotypic manifestations of Lowe syndrome.
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC H3C 3J7, Canada.
authors.forename: Khaled
authors.initials: K
authors.lastname: Ben El Kadhi
authors.forename: Chantal
authors.initials: C
authors.lastname: Roubinet
authors.forename: Sara
authors.initials: S
authors.lastname: Solinet
authors.forename: Grégory
authors.initials: G
authors.lastname: Emery
authors.forename: Sébastien
authors.initials: S
authors.lastname: Carréno
mesh_terms: D000818:Animals; D048749:Cytokinesis; D004330:Drosophila; D006706:Homeostasis; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D010744:Phosphoric Monoester Hydrolases