Function of cortical domains of the endoplasmic reticulum

真核细胞使用分泌（SEC）途径用于质膜蛋白的生物合成。我们最近的研究与模式生物酿酒酵母表明，存在一个替代途径的运输的一个完整的膜蛋白质膜。蛋白Ist 2 p从内质网（ER）转运至细胞表面，与经典SEC途径的功能无关。我们已经确定了Ist 2 p（Ist 2c）的胞质C-末端结构域作为质膜的显性靶向信号。当该结构域位于其他膜蛋白的C-末端时，它将所得嵌合体重定向至质膜。由于这种机制主要是针对其他膜的蛋白质，我们假设，Ist 2 p的生物起源是由在ER的特定结构域的本地合成。最有可能的是，这些结构域位于细胞周边，蛋白质从那里通过未知的机制到达质膜。为了找到运输Ist 2 p所需的因子，我们将纯化Ist 2c相互作用蛋白，并进行遗传筛选，以确定这种新途径所需的基因。

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.