|Membrane Trafficking and Cell Division - CNRS URA2582|
|HEAD||Dr. Arnaud ECHARD / firstname.lastname@example.org|
|MEMBERS||Dr Arnaud ECHARD, Principal Investigator / Dr Laurent CHESNEAU, Post-doctoral fellow / Dr. Elizabeth CROWELL, Post-doctoral fellow / Ms. Daphné DAMBOURNET, PhD student / Mr. Mickaël MACHICOANE, PhD student / Ms. Murielle ROCANCOURT, technician / Mrs. Nadine DELARUE, secretary
Our group was created in 2010 and focuses on the role of membrane traffic, cytoskeletons and lipids in cell division, in particular during cytokinesis.
Cell division and thus cell proliferation 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, cytokinesis also has important consequences on the partitioning of the cytoplasm, intracellular organelles and, in the case of asymmetric cell divisions, of cortical cell fate determinants into the daughter cells. 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. Thus animal cell cytokinesis must be particularly robust.
Cytokinesis is driven by a stereotyped series of cell shape changes that are spatially and temporally regulated: cells round up at mitotic entry, then elongate along one axis in anaphase B, and cytokinesis starts with the contraction of a plasma membrane furrow at the mitotic spindle equator. Finally, daughter cells are connected for most of the duration of cytokinesis by an intercellular bridge that is eventually cut through a process called abscission.
Several genome-wide RNAi-based screens that we and others have carried out (e.g. Echard et al. Current Biology, 2004) revealed that intracellular membrane traffic played a key role in the late steps of cytokinesis. Membrane traffic allows selective transfer of membranes, lipids and proteins between intracellular compartments within eukaryotic cells. It is now apparent that deciphering the novel interface between cytokinesis and membrane traffic will be important to understand how cell division is achieved.
In order to identify which membrane trafficking pathways are specifically required for cytokinesis, we systematically studied which Rab GTPases are essential for cytokinesis. Indeed, small GTPases of the Rab superfamily are conserved key regulators of membrane trafficking in all eukaryotic cells and delineate specific intracellular transport pathways. Using RNAi-based screens in Drosophilaand human cells, we recently identified the Rab35 GTPase as essential for intercellular bridge stability as well as for normal cytokinesis abscission (Kouranti et al. Current Biology, 2006). We found that Rab35 regulates a distinct endocytic pathway, and promotes fast recycling of membranes from intracellular endosomes back to the plasma membrane. This appears important for normal septin cytoskeleton localization during cell division and late cytokinesis steps. We are currently studying how the Rab35 GTPase is temporally and spatially regulated, how this GTPase controls endocytosis, and by which molecular mechanisms it remodels cytoskeletons and lipids for successful cytokinesis. This will be important for understanding the general question of cell cortex polarization during cell division, and likely during immunological synapse formation, intracellular traffic of bacterial toxins, or phagocytosis.
Keywords: cytokinesis, cell division, membrane traffic, Rab GTPases, endocytosis, cytoskeleton
Miserey-Lenkei S, Chalancon G, Bardin S, Formstecher E, Goud B, Echard A. (2010)
Rab and actomyosin-dependent fission of transport vesicles at the Golgi complex. Nature Cell Biology: 12, 645-54. PMID: 20562865
Vielemeyer O., Nizak C., Jimenez AJ., Echard A., Goud B., Camonis J., Rain JC., Perez F. (2010). Characterization of single chain antibody targets through yeast two hybrid.
BMC BiotechnologyAug 22;10:59. PMID: 20727208
Activity Reports 2010 - Institut Pasteur
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