A Dual Role of ERGIC-localized Rabs in TMED10-mediated Unconventional Protein Secretion

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2024 Jun 26

PMID 38926505

Authors

Yuxin Sun

Xuan Tao

Yaping Han

Xubo Lin

Rui Tian

Haodong Wang

Pei Chang

Qiming Sun

Liang Ge

Min Zhang

Affiliations

Soon will be listed here.

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.

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