• The goal of our research is to elucidate mechanisms that regulate cytoskeletal remodelling during cell migration and axon guidance.
• Directed cell motility is essential for multicellular animal development, lymphocyte chemotaxis, and navigation of growing axons in the developing nervous system. Protrusion of a cell or growth cone toward attractive cues depends on activation of receptors that lead to an activation of Rho GTPases and in the case of chemotactic cells to an asymmetric distribution of specific phospholipids. Finally, the polymerization of actin filaments, a process regulated by several proteins including the MRL protein family (MIG-10, RIAM, Lamellipodin (Lpd), and Pico), the Ena/VASP family (Mena, VASP, EVL), N-WASP and the Arp2/3 complex, provides the force for plasma membrane protrusion.
• The work in our group focuses on signalling mechanisms that regulate the actin cytoskeleton downstream of growth factor and axon guidance receptors. We are utilizing live cell microscopy to analyze quantitatively the effects of genetically altered levels of signalling molecules on cytoskeletal dynamics, growth cone behaviour, cell polarity, and cell migration. Biochemical analysis of signalling complexes complements this analysis. 
• In the quest for molecules that link cell surface receptors to effectors of the actin cytoskeleton we have identified Lamellipodin (Lpd) as a novel Ena/VASP binding protein. Both proteins co-localize at the tips of lamellipodia and filopodia. Lpd contains a Ras association domain and a PH domain that binds specifically to PI(3,4)P2, an asymmetrically localized signal in chemotactic cells. 
• Overexpression of Lpd increases speed and reduces persistence of lamellipodial protrusion, in an Ena/VASP dependent fashion. Conversely, knockdown of Lpd expression leads to impairment in lamellipodia formation, reduction in velocity of residual lamellipodial protrusion and decrease in F-actin content. Furthermore Lpd and its fly ortholog Pico are required for EGF induced proliferation and this is mediated through the SRF transcription factor. Thus, Lpd may act as a key convergence point linking polarized phospholipid signals and small Ras GTPases with Ena/VASP proteins to regulate the actin cytoskeleton and cell proliferation.

Elucidation of mechanisms that regulate cytoskeletal remodelling during cell migration and axon guidance.

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