COMPARTMENTAL ORGANIZATION OF THE YEAST GOLGI COMPLEX

从酵母到人类细胞，高等细胞的一个显著特征是 它们的隔室组织形成膜结合的细胞器， 每一个都有独特的组成和功能。的总目标是 我们的研究计划是了解细胞如何组装 分泌途径的细胞器，特别是高尔基体 复合体，一个多隔室的细胞器，扮演着必不可少的角色 在蛋白质的运输、修饰和分选中的作用。 为了实现这一目标，蛋白质(Mnnlp)被 将对高尔基复合体的定位进行研究。酵母菌 这项工作将使用酿酒酵母，因为 ALL中分泌途径的基本相似性 真核细胞与强大的遗传和分子 酵母菌研究人员可用的方法使这种有机体 一个理想的模型系统。拟议的研究源于最近的 发现丝裂原活化蛋白(MAP)激酶的成员 族是Mnn1p高尔基体本地化所必需的。 这项建议的具体目的是：1)确定角色 猪MAPK通路在控制细胞周期中的作用 酵母高尔基复合体的隔室组织。2) 确定HOG途径外所需的蛋白质 曼尼普·高尔基的本地化。3)分析了Mnlp的作用机理。 高尔基本地化。4)确定COPII囊泡在 顺行蛋白通过高尔基复合体运输。它是 预计这些研究将产生更详细的 高尔基建筑群的隔间结构， 维持结构和结构所需的组成蛋白质 这种细胞器的功能，以及细胞用来 将蛋白质定位于高尔基复合体。 对人类健康有深远的影响，可以从 这项研究。无数的蛋白质，如生长因子和它们的 受体、免疫系统的蛋白质和病毒蛋白质都依赖于 关于要通过细胞运输的高尔基复合体，以进行分类 到适当的亚细胞域，并在翻译后 加工成最终的化学形式。细胞-细胞和细胞-矩阵 对正常发育很重要的相互作用，以及许多细胞-病原体 相互作用都涉及高尔基体中形成的碳水化合物表位 糖基转移酶。此外，特定高尔基体酶的丧失 活动导致几种严重的人类疾病，包括I- 细胞性疾病、假性Hurler多发性营养不良、HEMPAS病和LOWE 综合症。

A striking feature of higher cells, from yeast to human cells, is their compartmental organization into membrane-bound organelles, each with a unique composition and function. The overall goal of our research program is to understand how the cell assembles the organelles of the secretory pathway, particularly the Golgi complex, a multi-compartment organelle that plays an essential role in the transport, modification and sorting of proteins. Towards this goal, the mechanisms by which a protein (Mnnlp) is localized to the Golgi complex will be studied. The yeast Saccharomyces cerevisiae will be used for this work because of the fundamental similarity of the secretory pathway in all eukaryotic cells coupled with the powerful genetic and molecular approaches available to the yeast researcher make this organism an ideal model system. The proposed studies stem from the recent finding that members of a mitogen-activated protein (MAP) kinase family are required for Mnn1p Golgi localization. The specific aims of this proposal are to: 1) Define the role that the HOG MAP kinase pathway plays in controlling the compartmental organization of the yeast Golgi complex. 2) Identify proteins outside of the HOG pathway that are required for Mnnlp Golgi localization. 3) Analyze the mechanism of Mnnlp Golgi localization. 4) Define the role of COPII vesicles in anterograde protein transport through the Golgi complex. It is anticipated that these studies will result in a more detailed view of the compartmental structure of the Golgi complex, the constituent proteins required to maintain the structure and function of this organelle, and the mechanisms the cell uses to localize proteins to the Golgi complex. There are profound implications to human health that can be derived from this study. Innumerable proteins such as growth factors and their receptors, proteins of the immune system and viral proteins, all depend on the Golgi complex to be transported through the cell, to be sorted to the appropriate subcellular domain, and to be posttranslationally processed to their final chemical form. Cell-cell and cell-matrix interactions important for normal development, and many cell-pathogen interactions all involve carbohydrate epitopes formed in the Golgi by glycosyltransferases. In addition, loss of specific Golgi enzyme activities lead to several serious human disorders including I- cell disease, pseudo-Hurler polydystrophy, HEMPAS disease and Lowe syndrome.