Author: ["Daphné Dambournet","Mickael Machicoane","Laurent Chesneau","Martin Sachse","Murielle Rocancourt","Ahmed El Marjou","Etienne Formstecher","Rémi Salomon","Bruno Goud","Arnaud Echard"]
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Abstract
The PtdIns(4,5)P2 5-phosphatase OCRL, mutated in Lowe syndrome, is implicated in trafficking and associates with Rab GTPases. OCRL function is now extended to cytokinesis, where it controls abscission of the intercellular bridge downstream of Rab35 through the local reduction of both PtdIns(4,5)P2 levels and actin accumulation. 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 remodelling1,2,3,4,5,6. We previously identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages7. Here, we report that the phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) 5-phosphatase OCRL, which is mutated in Lowe syndrome patients8,9, 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.Cite this article
Dambournet, D., Machicoane, M., Chesneau, L. et al. Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat Cell Biol 13, 981–988 (2011). https://doi.org/10.1038/ncb2279 