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.

粗糙的内质网（ER）用作进入新近合成的激素和酶的分泌途径。因此，粗糙的ER介导了高效的易位从细胞质到其腔内的新生多肽。在组织中在需要高水平的分泌的地方，粗糙的ER非常丰富它占主导地位的细胞景观。 ER的扩散是响应中毒或细胞时，在细胞和组织中诱导被刺激以分泌大量蛋白质。是这里描述的研究目的是关注如何实现了粗糙ER的刺激增殖。结合核糖体代表粗糙ER的区别特征。一个哺乳动物粗糙的ER特异性蛋白，以前是分离的，并且特征是对核糖体具有高亲和力一级结构诱导粗膜增殖在酵母和哺乳动物细胞中的表达。有假设是导致ER膜增殖的特定信号通路可以现在使用生化，细胞的平衡在模型系统中进行测试生物学和遗传方法。将确定因素表征从酵母到哺乳动物的细胞上调的细胞上调他们的质量粗糙。初步结果表明，在酵母中，可以上调整个分泌途径，从而铺路调查这种复杂和重要的调节的方法在遗传牵引生物中的细胞内途径。