Abstract:
:Membrane fusion is generally controlled by Rabs, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), and tethering complexes. Syntaxin 17 (STX17) was recently identified as the autophagosomal SNARE required for autophagosome-lysosome fusion in mammals and Drosophila. In this study, to better understand the mechanism of autophagosome-lysosome fusion, we searched for STX17-interacting proteins. Immunoprecipitation and mass spectrometry analysis identified vacuolar protein sorting 33A (VPS33A) and VPS16, which are components of the homotypic fusion and protein sorting (HOPS)-tethering complex. We further confirmed that all HOPS components were coprecipitated with STX17. Knockdown of VPS33A, VPS16, or VPS39 blocked autophagic flux and caused accumulation of STX17- and microtubule-associated protein light chain (LC3)-positive autophagosomes. The endocytic pathway was also affected by knockdown of VPS33A, as previously reported, but not by knockdown of STX17. By contrast, ultraviolet irradiation resistance-associated gene (UVRAG), a known HOPS-interacting protein, did not interact with the STX17-HOPS complex and may not be directly involved in autophagosome-lysosome fusion. Collectively these results suggest that, in addition to its well-established function in the endocytic pathway, HOPS promotes autophagosome-lysosome fusion through interaction with STX17.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Jiang P,Nishimura T,Sakamaki Y,Itakura E,Hatta T,Natsume T,Mizushima Ndoi
10.1091/mbc.E13-08-0447subject
Has Abstractpub_date
2014-04-01 00:00:00pages
1327-37issue
8eissn
1059-1524issn
1939-4586pii
mbc.E13-08-0447journal_volume
25pub_type
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