期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 3, 页码 469-482出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.076489
关键词
Autophagy; Snare proteins; Early secretory pathway; Lysosomal compartment activity
类别
资金
- Wellcome Trust
- MRC
- Sackler Trust
- NIHR Biomedical Research Centre at Addenbrooke's Hospital
- The Daphne Jackson Trust
- Isaac Newton Trust
- Overseas Research Studentship
- Cambridge Trust Overseas
- Medical Research Council [G0600194, G120/952] Funding Source: researchfish
- MRC [G120/952, G0600194] Funding Source: UKRI
Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of intracellular organelles and long-lived proteins. Reduced autophagic activity has been shown to lead to the accumulation of misfolded proteins in neurons and might be involved in chronic neurodegenerative diseases. Here, we uncover an essential role for the syntaxin-5 SNARE complex in autophagy. Using genetic knockdown, we show that the syntaxin-5 SNARE complex regulates the later stages of autophagy after the initial formation of autophagosomes. This SNARE complex acts on autophagy by regulating ER-to-Golgi transport through the secretory pathway, which is essential for the activity of lysosomal proteases such as cathepsins. Depletion of syntaxin-5 complex components results in the accumulation of autophagosomes as a result of lysosomal dysfunction, leading to decreased degradation of autophagic substrates. Our findings provide a novel link between a fundamental process such as intracellular trafficking and human diseases that might be affected by defective biogenesis and/or homeostasis of the autophagosome-lysosome degradation system.
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