Wiedmann M, Huth A, Rapoport T A
Nature. 1984;309(5969):637-9. doi: 10.1038/309637a0.
Most secretory proteins are synthesized as precursor polypeptides carrying N-terminal, hydrophobic sequences which, by means of a signal recognition particle (SRP), trigger the membrane transfer of the polypeptide and are subsequently cleaved off. The signal sequences appear to be interchangeable between prokaryotes and eukaryotes. In bacteria, secretion only involves the crossing of a membrane, whereas in eukaryotes the secretory process can be separated into two distinct phases: translocation across the membrane of the rough endoplasmic reticulum and subsequent intraluminal transport by processes involving vesicle budding and fusion. Since secretory proteins must be distinguished from other soluble proteins destined for various sites in the reticular system, it is conceivable that eukaryotic secretory proteins possess additional markers distinct from the signal peptide to guide the polypeptide after its transfer through the membrane. Proteins are secreted at different rates from a eukaryotic cell, suggesting a role in intracellular transport for receptors with differing affinities for some topogenic features in secretory proteins. We have tested this possibility by introducing into the lumen of eukaryotic rough endoplasmic reticulum a prokaryotic protein which, by virtue of its origin, had not been adapted to the eukaryotic secretory pathway. We reasoned that secretion of the bacterial protein would indicate that after membrane transfer no topogenic signal(s) and corresponding recognition system(s) are required. We report here that this is indeed the case.
大多数分泌蛋白最初是以前体多肽的形式合成的，这些前体多肽带有N端疏水序列，该序列借助信号识别颗粒（SRP）触发多肽的膜转移，随后被切除。原核生物和真核生物的信号序列似乎是可互换的。在细菌中，分泌仅涉及穿过细胞膜，而在真核生物中，分泌过程可分为两个不同阶段：穿过糙面内质网的膜以及随后通过涉及囊泡出芽和融合的过程进行腔内运输。由于分泌蛋白必须与其他定位于网状系统不同部位的可溶性蛋白区分开来，可以想象真核生物分泌蛋白具有不同于信号肽的其他标记物，以便在多肽穿过膜后引导它。蛋白质从真核细胞中以不同速率分泌，这表明对分泌蛋白中某些拓扑特征具有不同亲和力的受体在细胞内运输中发挥作用。我们通过将一种原核蛋白导入真核糙面内质网腔来测试这种可能性，该原核蛋白因其来源未适应真核生物分泌途径。我们推断细菌蛋白的分泌将表明在膜转移后不需要拓扑信号和相应的识别系统。我们在此报告情况确实如此。
