REGULATED PROTEIN DELIVERY TO THE PLASMA MEMBRANE

细胞调控的一个重要方面是受控递送 将蛋白质运输到质膜，使细胞能够 利用小分子对细胞外信号做出反应。Dr。 Kaiser的研究小组提出了一种基因和 酿酒酵母的生化实验给出了基本的 对整体膜调控给药机制的认识 蛋白质进入质膜。Kaiser博士实验室最近的工作 已经表明，在酵母递送的一般氨基酸渗透酶 (Gap1)对质膜中氮源的响应 生长培养基。Gap1 Take细胞定位的调控 在跨高尔基体中，Gap1被加载到运输小泡中 定向到质膜或液泡。在这 应用，Kaiser博士建议阐明Gap1的机制 在跨高尔基山脉中分拣。这些研究将包括制定 体内和体外Gap1形成的检测方法 囊泡，以及基因产物的鉴定和表征 控制Gap1p排序的。 蛋白质对质膜的调节传递是关键 人类细胞生理学。例如，GLUT4葡萄糖 转运蛋白被输送到脂肪和肌肉细胞的质膜上 对胰岛素的反应，而这种受管制的贩运中的缺陷是 尽管这是非胰岛素依赖型糖尿病的根本原因。一点儿 已知控制GLUT4或其他基因位置的机制 人体内受调控的膜蛋白。然而，在酿酒酵母中 将有可能应用发达的基因的全部力量 生物体揭开负责调控的基因和蛋白质 在高尔基山脉中进行分类。来自酿酒酵母的基因应该能提供 到执行类似功能的哺乳动物基因，打开了 哺乳动物功能分类障碍诊断的新方法 细胞和提供新的机会来选择性地改变血浆 细胞膜的组成。

An important aspect of cell regulation is the controlled delivery of transport proteins to the plasma membrane, allowing the cells capacity to take up small molecules to respond to extracellular signals. Dr. Kaiser's research group proposes a combination of genetic and biochemical experiments in the yeast S. cerevisiae to give fundamental insight into the mechanism of regulated delivery of integral membrane proteins to the plasma membrane. Recent work in Dr. Kaiser's laboratory has shown that in yeast delivery of the general amino acid permease (Gap1) to the plasma membrane responds to the nitrogen source in the growth medium. The regulation of the cellular location of Gap1 takes place in the trans-Golgi where Gap1 is loaded into transport vesicles directed either to the plasma membrane or to the vacuole. In this application, Dr. Kaiser proposes to elucidate the mechanism of Gap1 sorting in the trans-Golgi. These studies will include development of in vivo and in vitro assays for the formation of Gap1-containing vesicles, and the identification and characterization of gene products that control Gap1p sorting. The regulated delivery of proteins to the plasma membrane is key to human cell physiology. For example, the GLUT4 glucose transporter is delivered to the plasma membrane of fat and muscle cells in response to insulin, and defects in this regulated trafficking are though to be a root cause of non-insulin- dependent diabetes. Little is known of the mechanisms that control the location of GLUT4 or other regulated membrane proteins in humans. However, in S. cerevisiae it will be possible to apply the full power of a well developed genetic organism to uncover the genes and proteins responsible for regulated sorting in the Golgi. The genes from S. cerevisiae should give access to the mammalian genes that perform similar functions, opening the way to new methods for the diagnosis of dysfunctional sorting in mammalian cells and providing new opportunities to selectively alter the plasma membrane composition of cells.