Abstract:
Transmembrane domains (TMDs) contain information targeting membrane proteins to various compartments of the secretory pathway. In previous studies, short or hydrophilic TMDs have been shown to target membrane proteins either to the endoplasmic reticulum (ER) or to the Golgi apparatus. However, the basis for differential sorting to the ER and to the Golgi apparatus remained unclear. To clarify this point, we quantitatively analyzed the intracellular targeting of a collection of proteins exhibiting a single TMD. Our results reveal that membrane topology is a major targeting element in the early secretory pathway: type I proteins with a short TMD are targeted to the ER, and type II proteins to the Golgi apparatus. A combination of three features accounts for the sorting of simple membrane proteins in the secretory pathway: membrane topology, length and hydrophilicity of the TMD, and size of the cytosolic domain. By clarifying the rules governing sorting to the ER and to the Golgi apparatus, our study could revive the search for sorting mechanisms in the early secretory pathway.
摘要:
跨膜结构域(TMD)包含将膜蛋白靶向分泌途径各个区室的信息。在以往的研究中,短的或亲水的TMD已被证明可以将膜蛋白靶向内质网(ER),或者高尔基体.然而,对ER和高尔基体进行差异分选的基础仍然不清楚。为了澄清这一点,我们定量分析了显示单个TMD的蛋白质集合的细胞内靶向。我们的结果表明,膜拓扑结构是早期分泌途径的主要靶向元件:具有短跨膜结构域的I型蛋白靶向ER,和II型蛋白质进入高尔基体。三个特征的组合说明了分泌途径中简单膜蛋白的分选:膜拓扑,TMD的长度和亲水性,和胞质结构域的大小。通过澄清对急诊室和高尔基体的排序规则,我们的研究可能会重新寻找早期分泌途径中的分选机制.