Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion

Szabolcs Takáts, Gábor Glatz, Győző Szenci, Attila Boda, Gábor V. Horváth, Krisztina Hegedűs, A. Kovács, G. Juhász

Research output: Article

13 Citations (Scopus)

Abstract

The autophagosomal SNARE Syntaxin17 (Syx17) forms a complex with Snap29 and Vamp7/8 to promote autophagosome-lysosome fusion via multiple interactions with the tethering complex HOPS. Here we demonstrate that, unexpectedly, one more SNARE (Ykt6) is also required for autophagosome clearance in Drosophila. We find that loss of Ykt6 leads to large-scale accumulation of autophagosomes that are unable to fuse with lysosomes to form autolysosomes. Of note, loss of Syx5, the partner of Ykt6 in ER-Golgi trafficking does not prevent autolysosome formation, pointing to a more direct role of Ykt6 in fusion. Indeed, Ykt6 localizes to lysosomes and autolysosomes, and forms a SNARE complex with Syx17 and Snap29. Interestingly, Ykt6 can be outcompeted from this SNARE complex by Vamp7, and we demonstrate that overexpression of Vamp7 rescues the fusion defect of ykt6 loss of function cells. Finally, a point mutant form with an RQ amino acid change in the zero ionic layer of Ykt6 protein that is thought to be important for fusion-competent SNARE complex assembly retains normal autophagic activity and restores full viability in mutant animals, unlike palmitoylation or farnesylation site mutant Ykt6 forms. As Ykt6 and Vamp7 are both required for autophagosome-lysosome fusion and are mutually exclusive subunits in a Syx17-Snap29 complex, these data suggest that Vamp7 is directly involved in membrane fusion and Ykt6 acts as a non-conventional, regulatory SNARE in this process.

Original languageEnglish
Article numbere1007359
JournalPLoS Genetics
Volume14
Issue number4
DOIs
Publication statusPublished - ápr. 1 2018

Fingerprint

SNARE Proteins
lysosomes
Lysosomes
protein
mutants
trafficking
defect
viability
amino acid
Lipoylation
membrane
Prenylation
Drosophila
Membrane Fusion
animal
amino acids
Autophagosomes
loss
mutant
SNARE proteins

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Takáts, S., Glatz, G., Szenci, G., Boda, A., Horváth, G. V., Hegedűs, K., ... Juhász, G. (2018). Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. PLoS Genetics, 14(4), [e1007359]. https://doi.org/10.1371/journal.pgen.1007359

Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. / Takáts, Szabolcs; Glatz, Gábor; Szenci, Győző; Boda, Attila; Horváth, Gábor V.; Hegedűs, Krisztina; Kovács, A.; Juhász, G.

In: PLoS Genetics, Vol. 14, No. 4, e1007359, 01.04.2018.

Research output: Article

Takáts, S, Glatz, G, Szenci, G, Boda, A, Horváth, GV, Hegedűs, K, Kovács, A & Juhász, G 2018, 'Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion', PLoS Genetics, vol. 14, no. 4, e1007359. https://doi.org/10.1371/journal.pgen.1007359
Takáts S, Glatz G, Szenci G, Boda A, Horváth GV, Hegedűs K et al. Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. PLoS Genetics. 2018 ápr. 1;14(4). e1007359. https://doi.org/10.1371/journal.pgen.1007359
Takáts, Szabolcs ; Glatz, Gábor ; Szenci, Győző ; Boda, Attila ; Horváth, Gábor V. ; Hegedűs, Krisztina ; Kovács, A. ; Juhász, G. / Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. In: PLoS Genetics. 2018 ; Vol. 14, No. 4.
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