Group on the Molecular and Cell Biology of Lipids and Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6R 2G3, Canada.
Institute of Atherosclerosis in Shandong First Medical University (Shandong Academy of Medical Sciences), Taian 271016, China.
J Mol Cell Biol. 2023 Feb 7;14(9). doi: 10.1093/jmcb/mjac063.
Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER-Golgi protein trafficking through a tubular network. Meanwhile, it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through COPI-coated vesicles. Surf4 can selectively mediate export of diverse cargos, such as PCSK9 very low-density lipoprotein (VLDL), progranulin, α1-antitrypsin, STING, proinsulin, and erythropoietin. It has been implicated in facilitating VLDL secretion, promoting cell proliferation and migration, and increasing replication of positive-strand RNA viruses. Therefore, Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target. However, the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive. Here, we summarize the most recent advances in Surf4, focusing on its role in lipid metabolism.
Surfeit 4 是一种多拓扑跨膜蛋白，主要位于内质网 (ER) 膜中。它广泛表达，作为货物受体发挥作用，通过经典的衣被蛋白复合物 II (COPII) 包被小泡或特定小泡介导货物从 ER 向高尔基体的运输。它还通过管状网络参与 ER-Golgi 蛋白运输。同时，它通过 COPI 包被小泡促进货物从高尔基体向 ER 的逆行运输。Surf4 可以选择性地介导多种货物的输出，如 PCSK9 极低密度脂蛋白 (VLDL)、颗粒蛋白前体、α1-抗胰蛋白酶、STING、胰岛素原和促红细胞生成素。它被认为有助于 VLDL 的分泌，促进细胞增殖和迁移，并增加正链 RNA 病毒的复制。因此，Surf4 在各种生理和病理生理过程中发挥着至关重要的作用，成为一个有前途的治疗靶点。然而，Surf4 如何选择性地对各种货物进行分类以进行 ER-Golgi 蛋白运输的分子机制仍不清楚。在这里，我们总结了 Surf4 的最新进展，重点介绍其在脂质代谢中的作用。
