Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila

Szabolcs Takáts, Karolina Pircs, Péter Nagy, Ágnes Varga, Manuéla Kárpáti, Krisztina Hegedus, Helmut Kramer, Attila L. Kovács, Miklós Sass, Gábor Juhász

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Homotypic fusion and vacuole protein sorting (HOPS) is a tethering complex required for trafficking to the vacuole/lysosome in yeast. Specific interaction of HOPS with certain SNARE (soluble NSF attachment protein receptor) proteins ensures the fusion of appropriate vesicles. HOPS function is less well characterized in metazoans. We show that all six HOPS subunits (Vps11 [vacuolar protein sorting 11]/CG32350, Vps18/Dor, Vps16A, Vps33A/ Car, Vps39/CG7146, and Vps41/Lt) are required for fusion of autophagosomes with lysosomes in Drosophila. Loss of these genes results in large-scale accumulation of autophagosomes and blocks autophagic degradation under basal, starvation-induced, and developmental conditions. We find that HOPS colocalizes and interacts with Syntaxin 17 (Syx17), the recently identified autophagosomal SNARE required for fusion in Drosophila and mammals, suggesting their association is critical during tethering and fusion of autophagosomes with lysosomes. HOPS, but not Syx17, is also required for endocytic down-regulation of Notch and Boss in developing eyes and for proper trafficking to lysosomes and eye pigment granules. We also show that the formation of autophagosomes and their fusion with lysosomes is largely unaffected in null mutants of Vps38/UVRAG (UV radiation resistance associated), a suggested binding partner of HOPS in mammals, while endocytic breakdown and lysosome biogenesis is perturbed. Our results establish the role of HOPS and its likely mechanism of action during autophagy in metazoans.

Original languageEnglish (US)
Pages (from-to)1338-1354
Number of pages17
JournalMolecular Biology of the Cell
Volume25
Issue number8
DOIs
StatePublished - Apr 15 2014

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Qa-SNARE Proteins
Lysosomes
Drosophila
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
SNARE Proteins
Protein Transport
Vacuoles
Mammals
Autophagy
Starvation
Autophagosomes
Down-Regulation
Yeasts
Radiation
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

Takáts, S., Pircs, K., Nagy, P., Varga, Á., Kárpáti, M., Hegedus, K., ... Juhász, G. (2014). Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. Molecular Biology of the Cell, 25(8), 1338-1354. https://doi.org/10.1091/mbc.E13-08-0449

Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. / Takáts, Szabolcs; Pircs, Karolina; Nagy, Péter; Varga, Ágnes; Kárpáti, Manuéla; Hegedus, Krisztina; Kramer, Helmut; Kovács, Attila L.; Sass, Miklós; Juhász, Gábor.

In: Molecular Biology of the Cell, Vol. 25, No. 8, 15.04.2014, p. 1338-1354.

Research output: Contribution to journalArticle

Takáts, S, Pircs, K, Nagy, P, Varga, Á, Kárpáti, M, Hegedus, K, Kramer, H, Kovács, AL, Sass, M & Juhász, G 2014, 'Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila', Molecular Biology of the Cell, vol. 25, no. 8, pp. 1338-1354. https://doi.org/10.1091/mbc.E13-08-0449
Takáts, Szabolcs ; Pircs, Karolina ; Nagy, Péter ; Varga, Ágnes ; Kárpáti, Manuéla ; Hegedus, Krisztina ; Kramer, Helmut ; Kovács, Attila L. ; Sass, Miklós ; Juhász, Gábor. / Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. In: Molecular Biology of the Cell. 2014 ; Vol. 25, No. 8. pp. 1338-1354.
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