Identification of septate junction proteins required for the integrity of the blood brain barrier

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We want to understand the formation and maintenance of the Drosophila blood brain barrier and have started to screen for mutants which are characterized by a leaky blood brain barrier. Using a dye injection protocol we have identified a small, presumably GPI linked membrane protein call Leaky. Further work showed that Leaky is required for the organization of glial septate junctions. Leaky belongs to a conserved protein family related to the CD59/Ly6 antigens. In the next funding period we aim to understand the molecular mechanisms how Leaky participates in the formation of septate junctions. Following a detailed phenotypic study on the subcellular Leaky protein distribution in wild type and different mutant backgrounds we want to identify possible Leaky ligands. In addition to the analysis of Leaky we plan to continue our screen for mutants affecting blood brain barrier function.