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SECRETORY PROTEIN TRANSLOCATION

分泌蛋白易位

基本信息

批准号：
6385682
负责人：
DAVID I MEYER
金额：
$ 29.23万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 2003-06-30
项目状态：
已结题

项目摘要

The rough endoplasmic reticulum (ER) serves as the entry point into the secretory pathway for newly-synthesized hormones and enzymes. Accordingly, the rough ER mediates highly-efficient translocation of nascent polypeptides from the cytoplasm into its lumen. In tissues where high levels of secretion are demanded, the rough ER is so abundant that it dominates the sub-cellular landscape. Proliferation of ER is induced in cells and tissues in response to intoxication, or when cells are stimulated to secrete large quantities of proteins. It is the purpose of the research described here to focus on the mechanism of how stimulated proliferation of the rough ER is accomplished. Bound ribosomes represent the distinguishing feature of rough ER. A mammalian rough ER-specific protein that was previously isolated and characterized as having a high-affinity for ribosomes and a remarkable primary structure induces rough membrane proliferation upon its expression in yeast and mammalian cells. The hypothesis that there is a specific signaling pathway leading to ER membrane proliferation can now be tested in model systems using a balance of biochemical, cell biological and genetic approaches. Factors will be identified and characterized that enable cells, from yeast to mammals, to upregulate their mass of rough ER. Preliminary results indicate that in yeast, it is possible to upregulate the entire secretory pathway, thus paving the way for an investigation of the regulation of this complex and important intracellular pathway in a genetically-tractable organism.

粗面内质网（ER）作为进入细胞的入口点。新合成的激素和酶的分泌途径。因此，粗糙ER介导了细胞质的高效易位。新生多肽从细胞质进入其内腔。组织中在需要高水平分泌的地方，粗面内质网是如此丰富，它主宰着亚细胞景观。 ER的增殖是诱导细胞和组织响应中毒，或当细胞被刺激分泌大量的蛋白质。是这里描述的研究目的是关注如何完成粗糙ER的刺激增殖。结合的核糖体代表了粗糙ER的显著特征。一哺乳动物粗糙ER特异性蛋白，其先前被分离，其特征在于对核糖体具有高亲和力，初级结构诱导粗糙膜增殖，在酵母和哺乳动物细胞中表达。假设有导致内质网膜增殖的特异性信号通路可以现在可以在模型系统中进行测试，生物学和遗传学方法。将确定各种因素，其特征在于能够使从酵母到哺乳动物的细胞上调他们的粗糙的急诊室的质量。初步结果表明，在酵母中，有可能上调整个分泌途径，从而铺平了调查这一复杂而重要的监管方式在遗传上易处理的生物体中的细胞内途径。