Diverse cellular strategies for the export of leaderless proteins

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.