Suzuki Tadashi, Lennarz William J
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo and PRESTO, Japan Science and Technology Corporation (JST), Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Glycobiology. 2002 Dec;12(12):803-11. doi: 10.1093/glycob/cwf095.
When glycoproteins formed in the endoplasmic reticulum (ER) are misfolded, they are generally translocated into the cytosol for ubiquitination and are subsequently degraded by the proteasome. This system, the so-called ER-associated glycoprotein degradation, is important for eukaryotes to maintain the quality of glycoproteins generated in the ER. It has been established in yeast that several distinct proteins are involved in this translocation and degradation processes. Small glycopeptides formed in the ER are exported to the cytosol in a similar manner. This glycopeptide export system is conserved from yeast to mammalian cells, suggesting its basic biological significance for eukaryotic cells. These two export systems (for misfolded glycoproteins and glycopeptides) share some properties, such as a requirement for ATP and involvement of Sec61p, a central membrane protein presumably forming a dislocon channel for export of proteins. However, the machinery of glycopeptide export is poorly understood. In this study, various mutants known to have an effect on export/degradation of misfolded glycoproteins were examined for glycopeptide export activity with a newly established assay method. Surprisingly, most of the mutants were found not to exhibit a defect in glycopeptide export. The only gene that was found to be required on efficient export of both types of substrates was PMR1, the gene encoding the medial-Golgi Ca(2+)/Mn(2+)-ion pump. These results provide evidence that although the systems involved in export of misfolded glycoproteins and glycopeptides share some properties, they have exhibited distinct differences.
当在内质网（ER）中形成的糖蛋白发生错误折叠时，它们通常会被转运到细胞质中进行泛素化，随后被蛋白酶体降解。这个系统，即所谓的内质网相关糖蛋白降解，对于真核生物维持内质网中产生的糖蛋白质量很重要。在酵母中已经确定，几种不同的蛋白质参与了这种转运和降解过程。在内质网中形成的小糖肽也以类似的方式输出到细胞质中。这种糖肽输出系统从酵母到哺乳动物细胞都是保守的，表明其对真核细胞具有基本的生物学意义。这两种输出系统（针对错误折叠的糖蛋白和糖肽）具有一些共同特性，例如需要ATP以及Sec61p的参与，Sec61p是一种核心膜蛋白，可能形成用于蛋白质输出的错位通道。然而，糖肽输出的机制还知之甚少。在这项研究中，使用新建立的检测方法，对各种已知会影响错误折叠糖蛋白输出/降解的突变体进行了糖肽输出活性检测。令人惊讶的是，大多数突变体在糖肽输出方面并未表现出缺陷。唯一被发现对两种类型底物的有效输出都必需的基因是PMR1，该基因编码高尔基体中部的Ca(2+)/Mn(2+)-离子泵。这些结果提供了证据，表明尽管参与错误折叠糖蛋白和糖肽输出的系统具有一些共同特性，但它们也表现出明显的差异。
