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

我们想要了解果蝇血脑屏障的形成和维持，并且已经开始筛选以漏血脑屏障为特征的突变体。使用染料注射方案，我们已经确定了一个小的，可能是GPI连接的膜蛋白称为Leaky。进一步的研究表明，Leaky对于胶质分离连接的组织是必需的。Leaky属于一个与CD59/Ly6抗原相关的保守蛋白家族。在下一个资助期，我们的目标是了解Leaky如何参与分离连接形成的分子机制。在对野生型和不同突变背景的亚细胞Leaky蛋白分布进行详细的表型研究后，我们希望确定可能的Leaky配体。除了对Leaky的分析，我们计划继续筛选影响血脑屏障功能的突变体。

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.