Mutations in the inner nuclear membrane protein emerin cause Emery-Dreifuss muscular dystrophy (EDMD). Although emerin can regulate both gene expression and nuclear structure, the molecular mechanisms by which mutations in emerin cause disease are not well understood. To begin determining the functions of emerin, the Wilson Lab has identified many novel emerin-binding proteins. One of these proteins, Lmo7, is a transcription factor that shuttles between the cell surface and the nucleus. Lmo7 is relevant to EDMD because loss of murine Lmo7 causes muscular dystrophy. To analyze Lmo7 function, I propose to identify cell surface and nuclear Lmo7-binding proteins using yeast two-hybrid and biochemical purification procedures, as well as test candidate proteins for binding. I will then create and characterize a panel of Lmo7 mutants to determine which sites in Lmo7 are required for protein binding. Next, I will test the hypothesis that Lmo7 regulates C2C12 myoblast differentiation by up- or down-regulating Lmo7 expression, and by expressing the Lmo7 mutants. Finally, I will test the hypothesis that Lmo7 transduces signals from the cell surface to the nucleus. These studies will provide novel insight into the mechanism of EDMD. ? ? ?
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