清华大学张敏等合作，近期取得重要工作进展。他们研究发现，ERGIC定位的Rabs在TMED10介导的非常规蛋白质分泌中发挥双重作用。相关研究成果2024年6月26日在线发表于《自然—细胞生物学》杂志上。

据介绍，货物跨膜转运是分泌的一个关键方面。在传统的分泌中，携带信号肽的蛋白质进入内质网（ER），而缺乏信号肽的一部分转运到内质网-高尔基体中间区室（ERGIC）。这一过程被称为非常规蛋白质分泌（UcPS）。UcPS中ERGIC的调节事件尚不清楚。

研究人员揭示了ERGIC定位的小GTP酶Rab1（Rab1A和Rab1B）和Rab2A在ERGIC上通过TMED10调节UcPS货物运输中的作用。Rab1增强TMED10转运蛋白的活性，促进货物转运到ERGIC中，而Rab2A与KIF5B合作，调节ERGIC的区室化，建立UcPS特异性区室。

总之，这一研究强调了ERGIC定位Rabs在控制货物转运和指定ERGIC在UcPS中功能方面的关键作用。

附：英文原文

Title: A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion

Author: Sun, Yuxin, Tao, Xuan, Han, Yaping, Lin, Xubo, Tian, Rui, Wang, Haodong, Chang, Pei, Sun, Qiming, Ge, Liang, Zhang, Min

Issue&Volume: 2024-06-26

Abstract: Cargo translocation across membranes is a crucial aspect of secretion. In conventional secretion signal peptide-equipped proteins enter the endoplasmic reticulum (ER), whereas a subset of cargo lacking signal peptides translocate into the ER–Golgi intermediate compartment (ERGIC) in a process called unconventional protein secretion (UcPS). The regulatory events at the ERGIC in UcPS are unclear. Here we reveal the involvement of ERGIC-localized small GTPases, Rab1 (Rab1A and Rab1B) and Rab2A, in regulating UcPS cargo transport via TMED10 on the ERGIC. Rab1 enhances TMED10 translocator activity, promoting cargo translocation into the ERGIC, whereas Rab2A, in collaboration with KIF5B, regulates ERGIC compartmentalization, establishing a UcPS-specific compartment. This study highlights the pivotal role of ERGIC-localized Rabs in governing cargo translocation and specifying the ERGIC’s function in UcPS.

DOI: 10.1038/s41556-024-01445-4

Source: https://www.nature.com/articles/s41556-024-01445-4