The overall goal of this project is to gain a detailed understanding of the molecular function of integrins. The PS integrins of Drosophila are very similar to vertebrate integrins, and provide a unique opportunity to examine integrin function in situ. Dr. Brower proposes to: 1). Define residues in the beta-PS integrin subunit that interact with extracellular ligands. This subunit is alternatively spliced, and data indicat that the domain encoded by the different fourth exons binds ligand directly. B site directed mutagenesis and a cell spreading assay, they will map specific integrin-ligand contacts. 2) Identify components that interact functionally with integrins, by screening for mutations in flies that can suppress the lethal effects of weak integrin mutations. 3) Elucidate molecular causes of th dominant wing blister phenotype (called Blistermaker) that results from overexpression of integrin subunits during pupal morphogenesis. This will be achieved primarily by overexpressing subunits with defined mutations as oppose to wild type proteins. 4) Identify components of the pathway that leads from integrin overexpression to wing blisters. The Blistermaker phenotype appears t result from defects in a regulatory pathway; by screening for suppressors of Blistermaker, they hope to uncover the steps in this pathway.
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