Function of cortical domains of the endoplasmic reticulum

内质网皮质结构域的功能

• 批准号: 20250808
• 负责人: Privatdozent Dr. Matthias Seedorf
• 金额: --
• 依托单位: Zentrum für Molekulare Biologie (ZMBH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/20250808?language=en
• 关键词: Function; cortical; domains; endoplasmic; reticulum

Eukaryotic cells use the secretory (SEC)-pathway for the biogenesis of plasma membrane proteins. Our recent studies with the model organism Saccharomyces cerevisiae have shown that an alternative pathway exists for the trafficking of an integral membrane protein to the plasma membrane. The protein Ist2p is transported from the endoplasmic reticulum (ER) to the cell surface independently of the function of the classical SEC-pathway. We have identified the cytosolic C-terminal domain of Ist2p (Ist2c) as a dominant targeting signal for the plasma membrane. When this domain is positioned at the C-terminus of other membrane proteins, it redirects the resulting chimeras to the plasma membrane. Since this mechanism operates dominantly over the targeting of proteins to other membranes, we postulate that the biogenesis of Ist2p is initiated by a local synthesis at specific domains of the ER. Most likely these domains are positioned at the cell periphery from where the protein travels by an unknown mechanism to the plasma membrane. In order to find the factors that are required for the trafficking of Ist2p, we will purify Ist2c-interacting proteins and perform a genetic screen to identify the required genes for this novel pathway.

真核细胞通过分泌（SEC）途径生成质膜蛋白。我们最近对模式生物酿酒酵母的研究表明，存在一种替代途径，可以将整体膜蛋白运输到质膜。Ist2p蛋白从内质网（ER）转运到细胞表面，独立于经典的sec途径的功能。我们已经确定Ist2p的胞质c端结构域（Ist2c）是质膜的主要靶向信号。当这个结构域位于其他膜蛋白的c端时，它将产生的嵌合体重定向到质膜。由于这种机制主要作用于蛋白质靶向其他膜，我们假设Ist2p的生物发生是由内质网特定区域的局部合成启动的。这些结构域很可能位于细胞外围，蛋白质通过一种未知的机制从那里到达质膜。为了找到Ist2p转运所需的因子，我们将纯化Ist2p相互作用蛋白，并进行遗传筛选，以确定这一新途径所需的基因。