Cytoskeleton in cell morphogenesis
Our team strives to understand the role of the actin cytoskeleton in membrane remodeling. The Arp2/3 complex is a molecular machine that creates branched actin networks, which are known to generate a force. This force participates in intracellular traffic and in membrane protrusion during cell migration. In this context, we are looking for novel regulators of the Arp2/3 complex using various screens in order to understand the different roles of branched actin networks in the cell.
We have recently obtained two successes: the identification of the WASH complex, which activates Arp2/3 at the surface of endosomes and the discovery of Arpin, an Arp2/3 inhibitory protein, which regulates cell migration. The WASH complex allows the generation of transport intermediates during endosomal sorting of receptors, such as integrins. Arpin antagonises membrane protrusions and allows cell turning.
We currently attempt to understand the role of these molecular machines in cancer development. Indeed, deregulation of tumor cell migration produces metastases. We have already uncovered the influence of these deregulations on patient survival.
Protrusion instability in fish keratocytes injected with Arpin (Dang et al., Nature 2013).
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.