A current view on molecular mechanisms and machineries driving unconventional pathways of protein secretion

2026-03-01

PRE

Yifei Pei

Ningning Guo

Min Zhang

Walter Nickel *

Liang Ge *

DOI：10.1016/j.ceb.2026.102632

Original

Original request for help

Save

Abstract

En 中文

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, GRASPdependent CUPS that enable starvation-induced Golgibypassing 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.

Keywords:

MEMBRANE PORE FORMATION

GASDERMIN D

ENDOPLASMIC-RETICULUM

GSDMD

TRANSLOCATION

TRAFFICKING

PYROPTOSIS

GRASP

A current view on molecular mechanisms and machineries driving unconventional pathways of protein secretion

Abstract

Journal

Organization

Cited Papers

Citing Papers