Plemper R K, Böhmler S, Bordallo J, Sommer T, Wolf D H
Institut für Biochemie der Universität Stuttgart, Germany.
Nature. 1997 Aug 28;388(6645):891-5. doi: 10.1038/42276.
Proteins enter the secretory pathway through the endoplasmic reticulum, which delivers properly folded proteins to their site of action and contains a quality-control system to monitor and prevent abnormal proteins from being delivered. Many of these proteins are degraded by the cytoplasmic proteasome, which requires their retrograde transport to the cytoplasm. Based on a co-immunoprecipitation of major histocompatibility complex (MHC) class I heavy-chain breakdown intermediates with the translocon subunit Sec61p, it was speculated that Sec61p maybe involved in retrograde transport. Here we present functional evidence from genetic studies that Sec61p mediates retrograde transport of a mutated lumenal yeast carboxypeptidase ycsY (CPY*) in vivo. The endoplasmic reticulum lumenal chaperone BiP (Kar2p) and Sec63p, which are also subunits of the import machinery, are involved in export of CPY* to the cytosol. Thus our results demonstrate that retrograde transport of proteins is mediated by a functional translocon. We consider the export of endoplasmic reticulum-localized proteins to the cytosol by the translocon for proteasome degradation to be a general process in eukaryotic cell biology.
蛋白质通过内质网进入分泌途径，内质网将正确折叠的蛋白质输送到其作用位点，并包含一个质量控制系统，以监测和防止异常蛋白质被输送。其中许多蛋白质被细胞质蛋白酶体降解，这需要它们逆向转运到细胞质中。基于主要组织相容性复合体（MHC）I类重链分解中间体与转运体亚基Sec61p的共免疫沉淀，推测Sec61p可能参与逆向转运。在这里，我们展示了来自遗传学研究的功能证据，即Sec61p在体内介导突变的内质网腔酵母羧肽酶ycsY（CPY*）的逆向转运。内质网腔伴侣BiP（Kar2p）和也是导入机制亚基的Sec63p参与了CPY*向细胞质的输出。因此，我们的结果表明，蛋白质的逆向转运是由功能性转运体介导的。我们认为，转运体将内质网定位的蛋白质输出到细胞质中进行蛋白酶体降解是真核细胞生物学中的一个普遍过程。
