Dr Arnaud ECHARD (Membrane Traffic and Cell Division Lab, Institut Pasteur - CNRS, Paris, France) has given a seminar on April 17, 2012 entitled: "Lipid and F-actin remodeling for successful cell division: Connections to the Lowe syndrome".
Date: Tuesday, 17 April 2012
Time: 9:00 a.m. - 11:00 a.m.
Venue: Ms Chen Yang Foo Oi Telemedicine Centre, 2/F, William M W Mong Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong
Abstract:
Cytokinesis leads to the physical separation of the daughter cells, and is characterized in animal cells by a complex series of cell shape changes and membrane remodeling. Following furrow ingression, daughter cells are connected for most of cytokinesis by an intercellular bridge, which is cut in a final step termed abscission. Cytoskeleton and lipid composition are profoundly remodeled during late cytokinesis steps, but how this occurs and whether it is important for successful cytokinesis remains to be established.
Growing evidence indicate that membrane traffic has a key contribution in the post-furrowing steps of cytokinesis. In order to identify more precisely the transport routes involved and how they function in cytokinesis, we previously conducted a systematic RNAi screen focused on Rab genes [1]. Rab proteins are key conserved GTPases that control membrane trafficking in eukaryotic cells, by regulating vesicle fusion, targeting and, as we reported recently, vesicle formation [2]. We found that Rab35 regulates an endocytic pathway and is involved in the initial stability of the intercellular bridge, after furrow contraction, by controlling the proper localization of SEPTIN2 in human cells. In addition, we noticed that Rab35 depletion led to additional cytokinesis defects characterized by either delayed or inhibited abscission [1].
I will present the molecular mechanism by which the Rab35 GTPase regulates lipid and cytoskeleton remodeling in terminal cytokinesis steps. We found that Rab35 controls the localization in late intercellular bridges of OCRL, a PI(4,5)P2 phosphatase. Our results indicate that PI(4,5)P2 hydrolysis is a key requirement for local removal of cortical F-actin and therefore normal cytokinesis abscission [3]. I will also discuss how these findings shed new light on the pleiotropic phenotypes associated with a disease, the Oculo-Cerebro-Renal syndrome of Lowe, in which this phosphatase is mutated. Finally, I will present how the Rab35 GTPase itself is regulated by an original ARF/Rab GTPase cascade that we recently discovered [4].
[1] Kouranti et al. Current Biology, 2006 [2] Miserey-Lenkei et al. Nature Cell Biology, 2010 [3] Dambournet et al. Nature Cell Biology, 2011 [4] Chesneau et al., Current Biology, 2012
Croucher-Pasteur Exchange Programme:
In collaboration with the International Affairs Department of Institut Pasteur and the Croucher Foundation, the Centre is establishing an exchange programme for students and post-doctoral fellows resident in Hong Kong in order to strengthen the scientific collaboration between Hong Kong and France. A 2 to 3 year scholarship covering travel, living and university registration expenses will be available for students and post-doctoral fellows resident in Hong Kong wishing to perform research work in laboratories of Institut Pasteur Paris. A lecture series of Pasteur scientists is organised to enable Hong Kong students to meet personally principal investigators from Institut Pasteur, know their scientific work and prospects of pursuing scientific work in their laboratories.