GENETICS OF ENDOCYTIC TRAFFICKING IN THE DROSOPHILA EYE

成年人的神经元基本上是不可替代的，特别容易受到 蛋白质聚集体的积累，功能失调的线粒体，以及类似的分心 剂.神经元限制这种损伤的最重要途径是 自噬这一途径最初在mTOR调节的细胞内表达。 启动酵母和哺乳动物细胞中饥饿诱导的代谢拯救途径 通过隔离膜的形成，随后其膨胀， 细胞质内容物进入封闭的自噬体并融合到溶酶体， 自噬体含量的降解。除了在饥荒中的重要性， 反应，饥饿和mTOR独立的自噬越来越被认为是一种 重要的质量控制机制，减少神经元的退化， 光感受器细胞，并与癌症和传染病有关。因此，我们认为， 不同的细胞信号通路调节自噬的速率， 生理学是很重要的。因为过度的自噬对细胞是致命的， 诱导自噬的不同信号通路必须仔细协调， 已校准。对于一个这样的途径，腺泡蛋白是作为一个关键的调节器。的 腺泡蛋白整合多种信号通路调节核心蛋白的功能 自噬蛋白和刺激诱导饥饿非依赖性自噬。 该基金旨在了解调节痤疮水平的分子机制， 蛋白质及其活性。为此，在目标1中，我们建议定义上游 腺泡的调节因子，包括负责调节 并探索它们作为可能药物靶点的潜力。在第二章中，我们将分析 腺泡与其效应子Atg 1（主调节激酶）之间的机制联系 自噬途径的一部分。在目标3中，我们将探讨 在视觉系统中破坏Acn-Atg 1信号模块。

Neurons in adults are essentially irreplaceable and especially vulnerable to the accumulation of protein aggregates, dysfunctional mitochondria, and similarly distractive agents. The most important pathway available to neurons to limit such damage is autophagy. This pathway, initially described in the context of the mTor-regulated starvation-induced metabolic rescue pathway in yeast and mammalian cells, is initiated by the formation of an isolation membrane followed by its expansion, the engulfment of cytoplasmic content into a closed autophagosome and its fusion to the lysosomes and degradation of autophagosomal content. Beyond its importance in the starvation response, starvation and mTor-independent autophagy is increasingly recognized as an important quality control mechanism that reduces degeneration of neurons and photoreceptor cells and has implications for cancer and infectious diseases. Therefore, the distinct cellular signaling pathways that adjust the rate of autophagy to the cell’s physiology are important to understand. Because excessive autophagy is lethal to cells, the different signaling pathways inducing autophagy must be careful coordinated and calibrated. For one such pathway, the Acinus protein is as a critical regulator. The Acinus protein integrates signals from multiple pathways to modulate the function of core autophagy proteins and stimulate the induction of starvation-independent autophagy. This grant aims to understand the molecular mechanisms that regulate the levels of Acn protein and its activity. For this purpose, in Aim 1, we propose to define upstream regulators of Acinus including the phosphatases and kinases responsible for regulating its activity and explore their potential as possible drug targets. In Aim 2, we will analyze the mechanistic link between Acinus and its effector Atg1, the master regulatory kinase of the autophagy pathway. In Aim 3, we will explore physiological consequences of disrupting the Acn-Atg1 signaling module in the context of visual system.