Cell Adhesion

Cell adhesion

team-item

Head of unit

Ivan de Curtis

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Cell migration and invasion require the dynamic coordination of adhesion, cytoskeletal organization, as well as protein and membrane traffic at the leading edge of the cell. Similar processes are involved in the migration of growth cones and in the establishment of synapses during neuronal development. Our major interest is the identification and analysis of the molecular mechanisms driving the protrusive activity at the edge of migrating cells and in developing neurons. We have identified novel molecular networks that are implicated in these processes. These networks include scaffold proteins, regulators and effectors of small GTPases of the Rho and Arf families. By using both in vitro and in vivo approaches, we are aiming at characterizing fundamental cellular mechanisms underlying cell motility events relevant to both physiological and pathological conditions.

Research activity

We are studing the assembly, function and dynamics of plasma membrane-associated platforms (PMAPs), which are supramolecular networks that assemble during protrusion at the front of migrating cells and near invadosomes. PMAPs are highly dynamic structures and are made of proteins that contain intrinsically disordered regions; they are required for tumor cell invasion and growth cone motility. For the functional analysis of PMAPs we combine bioinformatics, biochemical and structural approaches, with functional in vitro and in vivo assays to explore motility, and single molecule analysis on purified proteins by electron microscopy, with high resolution imaging for intracellular molecular dynamics and FRAP analysis in living cells. 

A second line of research is on the mechanisms that drive the development and function of cortical GABAergic interneurons. We use transgenic mice with knockout for Rac GTPases in combination with a novel protocol to obtain long-term cultures of purified interneurons from WT and KO animals, which has been recently setup in the laboratory. These experimental systems are used in parallel to address the molecular mechanisms that drive the development of functional inhibitory networks within the brain, and are relevant to neuropsychiatric diseases.