Enabled, a regulator of adhesion and cell motility

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): During development intercellular adhesion and the cytoskeleton must be regulated to accommodate the changes in cell shape, cell rearrangements and cell migrations that occur as the embryo is shaped. If they are not properly regulated, morphogenesis is disrupted and normal development fails. Furthermore, during the progression of most tumors, cell adhesion is reduced or lost, ultimately resulting in increased invasiveness and metastatic potential of the tumor. Recent studies have revealed that members of the Ena/VASP protein family not only promote cell adhesion, but also inhibit cell motility by regulating localized actin polymerization. Accordingly, both overexpression and depletion of one of the family members, VASP, leads to neoplastic transformation of fibroblasts. The continued study Ena/VASP function may therefore provide insight into the cellular mechanisms that underlie both morphogenesis and tumorigenesis. However, the presence of three Ena/VASP family members in mammals makes functional studies of these proteins in an intact animal difficult. To circumvent this, the function of Ena/VASP proteins will be examined in the fruit fly, Drosophila, where a single-family member, Enabled (Ena), is expressed. Ena functions during epithelial morphogenesis and cell migration will be defined by examining the consequences of loss of Ena function and Ena overexpression. The proposed role of Ena in promoting actin polymerization during epithelial morphogenesis will also be addressed using cell biological and genetic techniques. Finally, regulators and targets of Ena will be identified using a genetic modifier screen and their function during development characterized.