The Vici Syndrome Protein EPG5 Is a Rab7 Effector that Determines the Fusion Specificity of Autophagosomes with Late Endosomes/Lysosomes
Open accessAbstract
Mutations in the human autophagy gene EPG5 cause the multisystem disorder Vici syndrome. Here we demonstrated that EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. EPG5 is recruited to late endosomes/lysosomes by direct interaction with Rab7 and the late endosomal/lysosomal R-SNARE VAMP7/8. EPG5 also binds to LC3/LGG-1 (mammalian and C. elegans Atg8 homolog, respectively) and to assembled STX17-SNAP29 Qabc SNARE complexes on autophagosomes. EPG5 stabilizes and facilitates the assembly of STX17-SNAP29-VAMP7/8 trans-SNARE complexes, and promotes STX17-SNAP29-VAMP7-mediated fusion of reconstituted proteoliposomes. Loss of EPG5 activity causes abnormal fusion of autophagosomes with various endocytic vesicles, in part due to elevated assembly of STX17-SNAP25-VAMP8 complexes. SNAP25 knockdown partially suppresses the autophagy defect caused by EPG5 depletion. Our study reveals that EPG5 is a Rab7 effector involved in autophagosome maturation, providing insight into the molecular mechanism underlying Vici syndrome.
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EPG5 is an autophagy-related gene essential for the formation of degradative autolysosomes.
“EPG5 (FC = −1.12, p = 0.05) is an autophagy-related gene which is essential for the formation of degradative autolysosomes [162].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [162]
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- Authors
- Wang, Z., Miao, G., Xue, X., Guo, X., Yuan, C., Wang, Z., Zhang, G., Chen, Y., Feng, D., Hu, J., & Zhang, H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Nankai University (CN)
- Peking University (CN)
- Guangdong Medical College (CN)
- Corresponding author
- Zhang, Hong
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 63
- Issue
- 5
- Pages
- 781-795
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2511744821
- Cited by
- 321
- References
- 30
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 41 · 2023: 26 · 2022: 34 · 2021: 26 · 2020: 37 · 2019: 42 · 2018: 34 · 2017: 21 · 2016: 2
- FWCI
- 30.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- EPG5, Vici syndrome, autophagosome maturation, autophagosome-lysosome fusion, late endosomes, SNARE complex, STX17, SNAP29, VAMP7, VAMP8, SNAP-25, LC3, autophagy
- MeSH terms
- Autophagosomes, Autophagy-Related Proteins, rab7 GTP-Binding Proteins, Amino Acid Sequence, Animals, Autophagy, Cataract, Gene Expression Regulation, HeLa Cells, Humans, Lysosomes, Membrane Fusion, Microtubule-Associated Proteins, Protein Binding, Proteins, Endosomes, Signal Transduction, Sequence Alignment, Caenorhabditis elegans, Sequence Homology, Amino Acid, rab GTP-Binding Proteins, Caenorhabditis elegans Proteins, Vesicular Transport Proteins, R-SNARE Proteins, Qa-SNARE Proteins, Qb-SNARE Proteins, Qc-SNARE Proteins, Synaptosomal-Associated Protein 25, Lysosomal Membrane Proteins, Agenesis of Corpus Callosum
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