GENETICS OF ENDOCYTIC TRAFFICKING IN THE DROSOPHILA EYE

内体区室具有多种功能。除了他们的经典角色， 将内化的货物运送到溶酶体用于营养目的和用于下- 调节细胞表面受体，它们还用于将生物合成货物引导至 不同的溶酶体相关细胞器。内吞运输的调节也是 与自噬密切相关，自噬构成了溶酶体的第二条递送途径。 该途径完成细胞内组分的吞噬， 自噬体最终与溶酶体融合以降解其内容物。 自噬可能是细胞对蛋白质积累最重要的防御机制。 受损和聚集的蛋白质以及功能失调的细胞器。干扰 自噬加速眼睛或其他组织的退化过程， 与癌症有关果蝇构成了一个很好的模型系统来分析一部小说 连接自噬调节和内吞运输的途径。的 dAcinus蛋白调节内吞运输并增强EGF和 Notch受体。dAcinus对于自噬体的正常成熟也是必需的 而增加的dAcinus水平诱导自噬。目标1建议使用基因 和转基因方法，以确定哪些细胞外信号负责 不同方面的动态调节dAcinus在发展中的眼睛。目标2将 分析dAcinus蛋白中的哪些元件在上下文中介导其调节 内吞运输和自噬。目的3将确定哪些靶点在内吞作用中 运输和自噬由dAcinus功能调节，使用下一个 代测序和遗传方法。

Endosomal compartments have diverse functions. In addition to their classic role in delivering internalized cargo to lysosomes for nutritional purposes and for the down- regulation of cell surface receptors, they also serve to direct biosynthetic cargo to a diverse set of lysosome-related organelles. The regulation of endocytic trafficking is also closely linked to autophagy which constitutes a second delivery pathway to lysosomes. This pathway accomplishes the engulfment of intracellular components into autophagosomes which ultimately fuse with lysosomes to degrade their content. Autophagy may be the most important defense cells have against the accumulation of damaged and aggregated proteins and dysfunctional organelles. Interference with autophagy hastens degenerative processes in the eye or other tissues and has also been linked to cancer. Drosophila constitutes an excellent model system to analyze a novel pathway that links the regulation of autophagy to that of endocytic trafficking. The dAcinus protein modulates endocytic trafficking and enhances signaling by the EGF and Notch receptors. dAcinus is also necessary for the normal maturation of autophagosomes whereas increased levels of dAcinus induce autophagy. Aim 1 proposes to use genetic and transgenic approaches to determine which extracellular signals are responsible for the different aspects of the dynamic regulation of dAcinus in the developing eye. Aim 2 will analyze which elements within the dAcinus protein mediate its regulation in the context of endocytic trafficking and autophagy. Aim 3 will determine which targets in endocytic trafficking and autophagy are regulated by dAcinus function using a combination of next generation sequencing and genetic approaches.