Identification of factors that regulate AP3-dependent transport

细胞由许多不同的隔室组成，每个隔室执行不同的功能。例如，“溶酶体”可以被认为是细胞的回收中心，因为它含有分解不需要的蛋白质的酶，因此它们的成分可以重新用于制造新的蛋白质。除了清除不需要的分子外，特殊类型的溶酶体还充当免疫、凝血和大脑功能所需蛋白质的储存室。 在溶酶体内回收蛋白质的酶首先在称为“高尔基体”的不同隔室中制造。然后这些酶从高尔基体转移到溶酶体的小容器中，称为“囊泡”。 将正确的蛋白质分选到正确的囊泡中非常重要，因此可以将其递送到正确的位置。这项任务通常由一组称为衔接蛋白复合物的蛋白质完成，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。 一种特殊类型的衔接蛋白复合物AP-3是溶酶体形成和功能所必需的。然而，衔接蛋白不能自己工作。其他类型的适配器具有引导它们到正确位置并激活它们进行货物结合的调节器，但到目前为止还没有发现AP-3的调节器。我们使用酵母作为模型系统来识别这些调节器并了解它们如何工作。虽然酵母是一种简单的生物体，但酵母AP-3调节的途径与液泡（人类溶酶体的酵母版本）惊人地相似。因此，酵母是一个很好的资源，用于识别参与人类复杂运输途径的基因。酵母基因组的简单性质也使我们能够获得所有合作调节细胞途径的基因的“快照”视图。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.