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  • A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion.

A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion.

Cell (2020-04-10)
Min Zhang, Lei Liu, Xubo Lin, Yang Wang, Ying Li, Qing Guo, Shulin Li, Yuxin Sun, Xuan Tao, Di Zhang, Xiachen Lv, Li Zheng, Liang Ge
ABSTRACT

Many cytosolic proteins lacking a signal peptide, called leaderless cargoes, are secreted through unconventional secretion. Vesicle trafficking is a major pathway involved. It is unclear how leaderless cargoes enter into the vesicle. Here, we find a translocation pathway regulating vesicle entry and secretion of leaderless cargoes. We identify TMED10 as a protein channel for the vesicle entry and secretion of many leaderless cargoes. The interaction of TMED10 C-terminal region with a motif in the cargo accounts for the selective release of the cargoes. In an in vitro reconstitution assay, TMED10 directly mediates the membrane translocation of leaderless cargoes into the liposome, which is dependent on protein unfolding and enhanced by HSP90s. In the cell, TMED10 localizes on the endoplasmic reticulum (ER)-Golgi intermediate compartment and directs the entry of cargoes into this compartment. Furthermore, cargo induces the formation of TMED10 homo-oligomers which may act as a protein channel for cargo translocation.

MATERIALS
Product Number
Brand
Product Description

Millipore
ANTI-FLAG® M2 Affinity Gel, purified immunoglobulin, buffered aqueous glycerol solution
Millipore
Monoclonal Anti-HA−Agarose antibody produced in mouse, clone HA-7, purified immunoglobulin, PBS suspension
Sigma-Aldrich
Aminopterin, powder