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Published on: December 17, 2013
A current view on molecular mechanisms and machineries driving unconventional pathways of protein secretion
Yifei Pei1, Ningning Guo2, Min Zhang1
1State Key Laboratory of Membrane Biology, Beijing, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
Abstract:
Unconventional protein secretion (UcPS) has emerged as a major route for exporting proteins that lack signal peptides and cannot enter the classical ER-Golgi pathway. UcPS comprises mechanistically diverse pathways involving either direct membrane translocation or vesicular intermediates. Direct export is exemplified by PI(4,5)P2-dependent FGF2 pore formation and gasdermin pores that release cytokines during pyroptosis. Vesicle-based routes include TMED-mediated translocation at the ER-Golgi intermediate compartment (ERGIC) feeding secretory autophagy carriers, GRASP-dependent CUPS that enable starvation-induced Golgi-bypassing secretion, and MAPS-mediated export of misfolded proteins via late endosomes. These pathways reveal a shared principle: cells deploy multiple, context-specific mechanisms to move proteins across membranes without classical signal peptides.
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