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

Autor: Sun Y; State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China., Tao X; State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China., Han Y; State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China., Lin X; Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine, Beihang University, Beijing, China., Tian R; Department of Biochemistry and Department of Cardiology of Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China., Wang H; State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China., Chang P; State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China., Sun Q; Department of Biochemistry and Department of Cardiology of Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China., Ge L; State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China. liangge@mail.tsinghua.edu.cn., Zhang M; State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China. zhangmin143@mail.tsinghua.edu.cn.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Jul; Vol. 26 (7), pp. 1077-1092. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1038/s41556-024-01445-4
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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