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 它们的隔室组织成膜结合的细胞器， 每一个都具有独特的组成和功能。 的总目标 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 复杂，多室细胞器，发挥重要作用， 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 将研究定位于高尔基复合体。 酵母 酿酒酵母将用于这项工作，因为 分泌途径的基本相似性， 真核细胞加上强大的遗传和分子 酵母研究人员可用的方法使这种生物体 一个理想的模型系统。 拟议的研究源于最近的 发现有丝分裂原活化蛋白（MAP）激酶 Mnn 1 p高尔基体定位所需的家族。 本建议的具体目标是：1）确定作用 HOG MAP激酶通路在控制 酵母高尔基复合体的分隔组织。（二） 识别HOG途径之外的蛋白质， 用于Mnnlp高尔基体定位。3)分析Mnnlp的机理 高尔基体定位。4)定义COPII囊泡的作用， 蛋白质通过高尔基复合体的顺行运输。 是 预计这些研究将导致更详细的 鉴于高尔基复合体的房室结构， 维持结构所需的组成蛋白质， 这个细胞器的功能，以及细胞用来 将蛋白质定位于高尔基复合体。 对人类健康有着深远的影响， 本研究生长因子及其衍生物等无数蛋白质 受体、免疫系统蛋白和病毒蛋白都依赖于 在高尔基复合体上被运送到细胞中， 到适当的亚细胞结构域， 加工成最终的化学形态 细胞-细胞和细胞-基质 对正常发育重要的相互作用，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- 细胞病、假性Hurler多营养不良、HEMPAS病和Lowe 综合征

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.