REVIEW

Diverse cellular strategies for the export of leaderless proteins

The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China

^* Corresponding author (email: liangge@mail.tsinghua.edu.cn)

Received: 12 April 2022
Revised: 26 April 2022
Accepted: 29 April 2022

Abstract

Unconventional protein export/secretion (UPE/UPS), in contrast to the classical ER-Golgi-dependent export/secretion of proteins with a leader sequence (signal peptide), employs multiple means to release leaderless cargoes (and in some special cases, cargoes with a leader sequence) to the extracellular space. By far, two major types of UPE have been classified, vesicle-independent UPE and vesicle-dependent UPE. In the former, UPE cargoes can directly translocate across the plasma membrane from the cytoplasm without the assistance of a vesicle carrier. In the latter, UPE cargoes translocate into the lumen of a vesicle which then delivers them out of the cell through membrane trafficking. Both types of UPE require multiple unconventional solutions to complete secretion. Here, we briefly discuss the multiple strategies for a UPE cargo release, focusing on two key steps of leaderless cargoes release in UPE: protein translocation and membrane trafficking.