Identification of factors that regulate AP3-dependent transport

细胞由许多不同的隔室组成，每个隔间执行不同的功能。例如，“溶酶体”可以被认为是细胞的循环中心，因为它含有分解不需要的蛋白质的酶，这样它们的成分就可以重新用于制造新的蛋白质。除了去除不需要的分子外，特殊类型的溶酶体还充当免疫、血液凝结和大脑功能所需蛋白质的储存室。 在溶酶体中循环蛋白质的酶首先是在一个不同的隔室中制造的，称为“高尔基体”。然后，这些酶在小容器中从高尔基体转移到溶酶体内，称为“囊泡”。正确的蛋白质被分拣到正确的囊泡中是非常重要的，这样它才能被送到正确的位置。这项任务通常由一组称为接头蛋白复合体的蛋白质完成，它们识别运输的货物分子，并启动将它们带到最终目的地的过程。 溶酶体的形成和功能需要一种特殊类型的接头蛋白复合体AP-3。然而，接头蛋白不能自行发挥作用。其他类型的适配器都有调节器来引导它们到正确的位置并激活它们进行货物绑定，但到目前为止还没有发现AP-3的调节器。我们使用酵母作为一个模型系统来识别这些调节器并了解它们是如何工作的。虽然酵母是一种简单的有机体，但酵母AP-3调节的途径与液泡(酵母版本的人类溶酶体)惊人地相似。因此，酵母菌是识别人类复杂运输途径中涉及的基因的极好资源。酵母基因组的简单性质也使我们能够获得所有协同调节细胞途径的基因的“快照”。这将告诉我们，人类中哪些基因也可能与AP-3一起工作，以及它们调节的途径可能如何导致溶酶体的形成。

The cell consists of many different compartments, each carrying out a distinct function. For example, the "lysosome" can be thought of as the cell's recycling centre, since it contains enzymes that break down unwanted proteins so their components can be re-used to make new proteins. In addition to getting rid of unwanted molecules, special types of lysosomes serve as storage compartments for proteins needed for immunity, blood clotting, and brain function. The enzymes that recycle proteins inside lysosomes are first manufactured in a different compartment called the "Golgi". These enzymes are then moved from the Golgi to the lysosome in small containers called "vesicles". It is very important that the correct protein is sorted into the right vesicle so it can be delivered to the right place. This task is generally fulfilled by a group of proteins, called Adaptor Protein complexes, which recognize cargo molecules for transport and initiate the process that will take them to their final destination. A specific type of Adaptor Protein complex, AP-3, is required for the formation and function of lysosomes. However, Adaptor Proteins cannot work by themselves. Other types of Adaptors have regulators that guide them to the correct location and activate them for cargo binding, but so far no regulators for AP-3 have been found. We use yeast as a model system to identify these regulators and understand how they work. Although yeast is a simple organism, the yeast AP-3 regulates a strikingly similar pathway to the vacuole, the yeast version of the human lysosome. As a result, yeast is an excellent resource for identifying the genes involved in the complex transport pathways that operate in humans. The simple nature of the yeast genome also allows us to obtain a 'snapshot' view of all the genes that are cooperating to regulate a cellular pathway. This will tell us which genes in humans might also work with AP-3, and how the pathway they regulate might lead to the formation of lysosomes.