Evolutionarily conserved role and physiological relevance of a STX17/Syx17 (syntaxin 17)-containing SNARE complex in autophagosome fusion with endosomes and lysosomes

Krisztina Hegedus, Szabolcs Takats, A. Kovács, G. Juhász

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Phagophores engulf cytoplasmic material and give rise to autophagosomes, double-membrane vesicles mediating cargo transport to lysosomes for degradation. The regulation of autophagosome fusion with endosomes and lysosomes during autophagy has remained poorly characterized. Two recent papers conclude that STX17/syntaxin 17 (Syx17 in Drosophila) has an evolutionarily conserved role in autophagosome fusion with endosomes and lysosomes, acting in one SNARE complex with SNAP29 (ubisnap in Drosophila) and the endosomal/ lysosomal VAMP8 (CG1599/Vamp7 in Drosophila). Surprisingly, a third report suggests that STX17 might also contribute to proper phagophore assembly. Although several experiments presented in the two human cell culture studies yielded controversial results, the essential role of STX17 in autophagic flux is now firmly established, both in cultured cells and in an animal model. Based on these data, we propose that genetic inhibition of STX17/Syx17 may be a more specific tool in autophagic flux experiments than currently used drug treatments, which impair all lysosomal degradation routes and also inactivate MTOR (mechanistic target of rapamycin), a major negative regulator of autophagy. Finally, the neuronal dysfunction and locomotion defects observed in Syx17 mutant animals point to the possible contribution of defective autophagosome clearance to various human diseases.

Original languageEnglish
Pages (from-to)1642-1646
Number of pages5
JournalAutophagy
Volume9
Issue number10
DOIs
Publication statusPublished - 2013

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Qa-SNARE Proteins
SNARE Proteins
Endosomes
Lysosomes
Drosophila
Autophagy
Sirolimus
Locomotion
Cultured Cells
Animal Models
Cell Culture Techniques
Membranes
Autophagosomes
Pharmaceutical Preparations

Keywords

  • Autophagosome
  • Autophagy
  • CG1599/Vamp7
  • Flux
  • Fusion
  • Lysosome
  • Neurodegeneration
  • Syntaxin 17
  • Ubisnap/SNAP29
  • VAMP8

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

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title = "Evolutionarily conserved role and physiological relevance of a STX17/Syx17 (syntaxin 17)-containing SNARE complex in autophagosome fusion with endosomes and lysosomes",
abstract = "Phagophores engulf cytoplasmic material and give rise to autophagosomes, double-membrane vesicles mediating cargo transport to lysosomes for degradation. The regulation of autophagosome fusion with endosomes and lysosomes during autophagy has remained poorly characterized. Two recent papers conclude that STX17/syntaxin 17 (Syx17 in Drosophila) has an evolutionarily conserved role in autophagosome fusion with endosomes and lysosomes, acting in one SNARE complex with SNAP29 (ubisnap in Drosophila) and the endosomal/ lysosomal VAMP8 (CG1599/Vamp7 in Drosophila). Surprisingly, a third report suggests that STX17 might also contribute to proper phagophore assembly. Although several experiments presented in the two human cell culture studies yielded controversial results, the essential role of STX17 in autophagic flux is now firmly established, both in cultured cells and in an animal model. Based on these data, we propose that genetic inhibition of STX17/Syx17 may be a more specific tool in autophagic flux experiments than currently used drug treatments, which impair all lysosomal degradation routes and also inactivate MTOR (mechanistic target of rapamycin), a major negative regulator of autophagy. Finally, the neuronal dysfunction and locomotion defects observed in Syx17 mutant animals point to the possible contribution of defective autophagosome clearance to various human diseases.",
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AU - Kovács, A.

AU - Juhász, G.

PY - 2013

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