RRC ID 29225
著者 Takáts S, Pircs K, Nagy P, Varga Á, Kárpáti M, Hegedűs K, Kramer H, Kovács AL, Sass M, Juhász G.
タイトル Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila.
ジャーナル Mol Biol Cell
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.
巻・号 25(8)
ページ 1338-54
公開日 2014-4-1
DOI 10.1091/mbc.E13-08-0449
PII mbc.E13-08-0449
PMID 24554766
PMC PMC3982998
MeSH Animals Autophagy / physiology Cell Line Down-Regulation Drosophila Drosophila Proteins / biosynthesis Drosophila Proteins / genetics Drosophila Proteins / metabolism Eye / embryology Eye Proteins / biosynthesis Lysosomal-Associated Membrane Protein 1 / metabolism Lysosomes / metabolism* Membrane Fusion* Membrane Glycoproteins / biosynthesis Mutation Phagosomes / metabolism* Pigment Epithelium of Eye / metabolism Qa-SNARE Proteins / metabolism* R-SNARE Proteins / genetics RNA Interference RNA, Small Interfering Receptors, Notch / biosynthesis Receptors, Peptide / biosynthesis Tumor Suppressor Proteins / genetics Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism*
IF 3.791
引用数 117
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ dLAMP[CPTI001775] (DGRC#115240) Syx17[LL06330] (DGRC#140948) Vps11[LL06553] (DGRC#141824) UVRAG[LL03097] (DGRC#141002)、12230R-1