Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland.
Manufacturing Science and Technologies, Biotech Department, Merck, Z.I. de l'Ouriettaz 150, 1170 Aubonne, Switzerland.
J Cell Sci. 2024 Aug 1;137(15). doi: 10.1242/jcs.261738. Epub 2024 Aug 8.
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.
跨膜结构域（TMD）包含将膜蛋白靶向分泌途径的各种隔室的信息。在以前的研究中，短的或亲水的 TMD 已被证明可将膜蛋白靶向内质网（ER）或高尔基体。然而，将膜蛋白靶向到 ER 和高尔基体的基础仍然不清楚。为了澄清这一点，我们定量分析了一组具有单个 TMD 的蛋白质的细胞内靶向。我们的结果表明，膜拓扑结构是早期分泌途径中的主要靶向元件：具有短 TMD 的 I 型蛋白被靶向到 ER，而 II 型蛋白被靶向到高尔基体。三个特征的组合解释了分泌途径中简单膜蛋白的分拣：膜拓扑结构、TMD 的长度和疏水性以及细胞质域的大小。通过阐明将膜蛋白靶向到 ER 和高尔基体的规则，我们的研究可以重新寻找早期分泌途径中的分拣机制。
