ArticleNature communications2021
mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Hexosamine Biosynthetic Pathway and Fatty Acid β-Oxidative Imbalance: A Key Mechanism by Which Abnormal Macrophage Lipophagy Promotes Atherosclerosis in Diabetes.Cardiovascular drugs and therapy · 2026Review
- LAPTM5 Downregulation-Driven VAMP8 Phosphorylation Impairs Autophagosome-Lysosome Fusion and Aggravates Septic Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A full-active phosphorus dendron-based nanomedicine alleviates ischemic stroke through multi-target immunomodulation and neuroprotection.Bioactive materials · 2026Article
- Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.JACC. Basic to translational science · 2026Review
- Targeting the senescence‒autophagy axis via p16Signal transduction and targeted therapy · 2026Article
- Indole-3-Propionic Acid Improves Alveolar Development Impairment via Targeting VAMP8-mediated SNAREs Complex Formation in Bronchopulmonary Dysplasia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- VAMP8 function reveals tight linkage between endocytic recycling and endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cross-regulation of autophagy and pyroptosis: a new perspective on the inflammatory microenvironment of atherosclerosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Rhein protects against renal aging and fibrotic injury by multiple targets through inhibition of TNF-α-mediated autophagy and necroptosis crosstalk.Frontiers in pharmacology · 2026Article
- Targeting the secretory autophagy-extracellular vesicle interface: fate decisions and translational opportunities.Frontiers in pharmacology · 2026Review
- Vamp8 modulates cerebral ischemia-reperfusion injury via the autophagy-lysosome pathway.Scientific reports · 2025Article
- Comprehensive profiling of immune cell infiltration and biomarker identification in intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2025Article
- VAMP proteins: molecular architects in disease pathogenesis and therapeutic innovation.Medical oncology (Northwood, London, England) · 2025Review
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
- Uncovering the Mechanisms of Intracellular Membrane Trafficking by Reconstituted Membrane Systems.Membranes · 2025Review
- Exploring druggable targets and inflammation-mediated pathways in cancer: a Mendelian randomization analysis integrating transcriptomic and proteomic data.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Function ofInternational journal of molecular sciences · 2025Article
- Targeted UDP-glucose ceramide glucosyltransferase stable overexpression induces a metabolic switch improving cell performance at high cell density.Frontiers in bioengineering and biotechnology · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTORC1) has been shown to regulate autophagy at different steps. However, how mTORC1 regulates the N-ethylmaleimide-sensitive protein receptor (SNARE) complex remains elusive. Here we show that mTORC1 inhibits formation of the SNARE complex (STX17-SNAP29-VAMP8) by phosphorylating VAMP8, thereby blocking autophagosome-lysosome fusion. A VAMP8 phosphorylation mimic mutant is unable to promote autophagosome-lysosome fusion in vitro. Furthermore, we identify SCFD1, a Sec1/Munc18-like protein, that localizes to the autolysosome and is required for SNARE complex formation and autophagosome-lysosome fusion. VAMP8 promotes SCFD1 recruitment to autolysosomes when dephosphorylated. Consistently, phosphorylated VAMP8 or SCFD1 depletion inhibits autophagosome-lysosome fusion, and expression of phosphomimic VAMP8 leads to increased lipid droplet accumulation when expressed in mouse liver. Thus, our study supports that mTORC1-mediated phosphorylation of VAMP8 blocks SCFD1 recruitment, thereby inhibiting STX17-SNAP29-VAMP8 complex formation and autophagosome-lysosome fusion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.