title: Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis.
abstract: Abscission is the least understood step of cytokinesis. It consists of the final cut of the intercellular bridge connecting the sister cells at the end of mitosis, and is thought to involve membrane trafficking as well as lipid and cytoskeleton remodelling. We previously identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages. Here, we report that the phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) 5-phosphatase OCRL, which is mutated in Lowe syndrome patients, is an effector of the Rab35 GTPase in cytokinesis abscission. GTP-bound (active) Rab35 directly interacts with OCRL and controls its localization at the intercellular bridge. Depletion of Rab35 or OCRL inhibits cytokinesis abscission and is associated with local abnormal PtdIns(4,5)P2 and F-actin accumulation in the intercellular bridge. These division defects are also found in cell lines derived from Lowe patients and can be corrected by the addition of low doses of F-actin depolymerization drugs. Our data demonstrate that PtdIns(4,5)P2 hydrolysis is important for normal cytokinesis abscission to locally remodel the F-actin cytoskeleton in the intercellular bridge. They also reveal an unexpected role for the phosphatase OCRL in cell division and shed new light on the pleiotropic phenotypes associated with Lowe disease.
authors.affiliation: Institut Pasteur, Membrane Traffic and Cell Division Lab. 25-28 rue du Dr Roux, 75724 Paris cedex 15, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Dambournet
authors.forename: Mickael
authors.initials: M
authors.lastname: Machicoane
authors.forename: Laurent
authors.initials: L
authors.lastname: Chesneau
authors.forename: Martin
authors.initials: M
authors.lastname: Sachse
authors.forename: Murielle
authors.initials: M
authors.lastname: Rocancourt
authors.forename: Ahmed
authors.initials: A
authors.lastname: El Marjou
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Arnaud
authors.initials: A
authors.lastname: Echard
mesh_terms: D000199:Actins / Q000378:metabolism*; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009800:Oculocerebrorenal Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D050505:Mutant Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; C511183:RAB35 protein, human; D020691:rab GTP-Binding Proteins