Beyond the Secretory Pathway: New Insights Into Protein Release

Journal article : Review

In eukaryotes, protein secretion plays essential roles in intercellular communications and extracellular niche‐building. Protein secretion generally requires a signal sequence that targets cargos to the canonical secretory pathway consisting of the endoplasmic reticulum (ER), the Golgi apparatus, plasma membrane, and vesicles moving between these compartments. However, cytoplasmic proteins lacking signal sequences (e.g., IL1β, Acb1, FGF2) have been detected, and many have defined functions in the extracellular space, suggesting unconventional protein secretion (UcPS) via alternative pathways. In recent years, scientists have uncovered many new UcPS paradigms, reporting a plethora of mechanisms that collectively form a new field. The inaugural Cold Spring Harbor Asia (CSHA) conference on “Molecular Mechanisms and Physiology of Unconventional Secretion” is the first meeting to bring these researchers together, providing a collegial platform for information sharing at this exciting frontier of cell biology research.

Authors: Chen, R; Costa‐Filho, AJ; Debnath, J; Galli, T; Ge, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Traffic: The moving front of cell biology
• Volume: 26
• Issue: 10-12
• Pages: e70022
• Article number: e70022
• Publication date: 2025-11-06
• Acceptance date: 2025-10-14
• DOI: 10.1111/tra.70022
• EISSN: 1600-0854
• ISSN: 1398-9219
• Language: English
• Keywords: stress adaptation; lysosome; autophagy; extracellular vesicle; unconventional protein secretion; CUPS
• Subtype: Review