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Séminaire impromptu - Arnaud Echard"Actin remodelling and cell division"

Abstract :

Une invitation de David Perrais de l'IINS.

Cell division ultimately relies on cytokinesis, which leads to the physical separation of the two daughter cells at the end of mitosis. Besides being essential for maintaining genomic stability and cell renewal, cytokinesis also has important consequences on the partitioning into the daughter cells of the cytoplasm, of intracellular organelles and, in the case of asymmetric cell divisions, of cortical cell fate determinants. It has recently been demonstrated that a single defect in cytokinesis could promote tumorigenesis in mice, and it now appears that cytokinesis failure has been overlooked as a fundamental cause of tumorigenesis and aneuploidy. Abscission is the final and 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 have identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages. Moreover, we show 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. These 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.

Selected publications

Crowell, E. F., Tinevez, J. Y., and Echard, A. (2013). A simple model for the fate of the cytokinesis midbody remnant: Implications for remnant degradation by autophagy: Modeling remnant production and degradation enables re-interpretation of published data and improves design of future experiments. Bioessays 35, 472-481.

Deschamps, C., Echard, A., and Niedergang, F. (2013). Phagocytosis and cytokinesis: do cells use common tools to cut and to eat? Highlights on common themes and differences. Traffic 14, 355-364.

Chesneau, L., Dambournet, D., Machicoane, M., Kouranti, I., Fukuda, M., Goud, B., and Echard, A. (2012). An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis. Curr Biol 22, 147-153.

Dambournet, D., Machicoane, M., Chesneau, L., Sachse, M., Rocancourt, M., El Marjou, A., Formstecher, E., Salomon, R., Goud, B., and Echard, A. (2011). Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis. Nat Cell Biol 13, 981-988.

Arnaud Echard

Group Leader: Dr. Arnaud Echard
“Membrane trafficking and cell division”,
Institut Pasteur, Paris.
PhD, CNRS Directeur de Recherche
arnaud.echard @