Genomic Medicine Institute, Lerner Research Institute of Cleveland Clinic, Cleveland, OH, U.S.A.
Biochem Soc Trans. 2023 Jun 28;51(3):971-981. doi: 10.1042/BST20220713.
Proteins that are destined to enter the secretory pathway are synthesized on the rough endoplasmic reticulum (ER) and then translocated into the ER lumen, where they undergo posttranslational modifications, folding, and assembly. After passing a quality control system, the cargo proteins are packaged into coat protein complex II (COPII) vesicles to exit the ER. In metazoans, most COPII subunits have multiple paralogs, enabling COPII vesicles the flexibility to transport a diverse range of cargo. The cytoplasmic domains of transmembrane proteins can interact with SEC24 subunits of COPII to enter the ER exit sites. Some transmembrane proteins may also act as cargo receptors that bind soluble secretory proteins within the ER lumen, enabling them to enter COPII vesicles. The cytoplasmic domains of cargo receptors also contain coat protein complex I binding motifs that allow for their cycling back to the ER after unloading their cargo in the ER-Golgi intermediate compartment and cis-Golgi. Once unloaded, the soluble cargo proteins continue maturation through the Golgi before reaching their final destinations. This review provides an overview of receptor-mediated transport of secretory proteins from the ER to the Golgi, with a focus on the current understanding of two mammalian cargo receptors: the LMAN1-MCFD2 complex and SURF4, and their roles in human health and disease.
在糙面内质网上合成的定位于分泌途径的蛋白质随后被转运到内质网腔中，在那里它们经历翻译后修饰、折叠和组装。在通过质量控制系统后，货物蛋白被包装到衣被蛋白复合物 II（COPII）小泡中以离开内质网。在后生动物中，大多数 COPII 亚基具有多个同源物，使 COPII 小泡具有运输多种货物的灵活性。跨膜蛋白的细胞质结构域可以与 COPII 的 SEC24 亚基相互作用，进入内质网出口部位。一些跨膜蛋白也可能作为货物受体，在内质网腔中结合可溶性分泌蛋白，使它们能够进入 COPII 小泡。货物受体的细胞质结构域也包含衣被蛋白复合物 I 结合基序，允许它们在将货物卸载到内质网-高尔基体中间池和顺面高尔基体后循环回到内质网。一旦卸载，可溶性货物蛋白在到达最终目的地之前，通过高尔基体继续成熟。本文综述了从内质网到高尔基体的受体介导的分泌蛋白运输，重点介绍了两种哺乳动物货物受体：LMAN1-MCFD2 复合物和 SURF4 及其在人类健康和疾病中的作用。
