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Cytoskeleton in cell morphogenesis
Group leader :Alexis Gautreau
Our team seeks to understand how the cell determines its shape and the morphology of its internal compartments. We know that cell membranes are remodeled by the actin cytoskeleton and the force it generates. The Arp2/3 complex, which contains two proteins related to actin, is a major nucleator of actin. It generates branched actin networks. These networks play an essential role in the formation of migration structures, where the plasma membrane is projected, and in membrane trafficking, where actin polymerization promotes fission of vesicles from various membrane compartments. The Arp2/3 complex is regulated by several multiprotein complexes. We try to characterize their cellular function and their regulatory mechanisms at the molecular level:
The WAVE complex activates the Arp2/3 complex at the plasma membrane in migration structures. This is the context in which we are interested in understanding its regulation. Activation of the WAVE complex has recently been reconstituted in vitro, but different screens in human or Drosophila cells (proteomics and RNAi screens) have allowed us to identify unsuspected new regulators that define new steps in its cycle of molecular activation. The aim of this research is to control cell migration in pathological conditions such as the metastasis formed by tumor cells.
Cells, whose morphology was controlled through adhesive micropatterns
The WASH complex activates the Arp2/3 complex at the surface of endosomes and thereby facilitates fission of vesicles ensuring the intracellular transport of various important molecules. By identifying the WASH complex, we found that it contained Strumpellin, the product of a gene mutated in patients affected by Hereditary Spastic Paraplegia (HSP), a genetic disease characterized by the degeneration of neurons that innervate muscles. We are currently examining how this super-multiprotein complex containing an activator of the Arp2/3 complex, an inhibitor of actin filament elongation and Strumpellin, among others, is architectured. In parallel, we are looking for protein and lipid ligands of the different subunits. These two endeavors should shed light on the mechanisms by which the WASH complex facilitates the fission of vesicles and on the pathophysiology of HSP.
Download our award-winning movie at the Cell Dance contest of the last ASCB meeting (San Diego, December 2009)
Main methods used: overexpression of genes in mammalian cells in culture, inactivation of genes by RNAi, microscopy and video-microscopy, purification of recombinant proteins, purification of multiprotein complexes, proteomics.
Année internationale de la cristallographie: des équipes du LEBS à la une
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