Neuroscience
Cell adhesion
Cell motility is necessary for physiological events such as the wiring of the nervous system, as well as for pathological conditions like tumor cell invasion. Cell motility is regulated by molecular networks that allow the coordination of adhesion, cytoskeletal organization, and molecular trafficking at the leading edge of motile cells.
Research activity
We are interested in the characterization of the mechanisms driving the protrusive activity at the edge of migrating cells and the formation of synapses in developing neurons. We are characterizing the function of a protein network that is shared in the regulation of protrusion during cell migration and invasion as well as in neuronal development. This network includes a core of scaffold proteins that interact with regulatory enzymes (small GTPases, kinases, phosphatases), to localize them at specific sites of the migrating cell or in developing neurons. The network under study forms plasma membrane-associated platforms (PMAPs) that specifically assemble near the front of migrating cells. High resolution imaging in living cells shows that PMAPs are dynamic. They are made of protein condensates that show liquid-like behavior. The study of protein condensates with liquid behavior is an exciting developing area of research, since they underlie the organization of several physiological and pathological processes in living organisms.
Our studies indicate that PMAPs are condensates essential to regulate protrusion during cell motility. To address their function, we combine biochemical-structural analysis, with high resolution imaging to follow dynamic molecular events in living cells, and quantitative assays to address their effects on cell motility and neuronal development. Our working model is that the liquid-like properties of PMAPs are important to recruit relevant proteins at specific sites and times in cells to regulate their behavior. The understanding of the mechanisms regulating assembly and disassembly of PMAPs is expected to highlight molecular players relevant to cell invasion and neuronal development.
