Atg9A trafficking through the recycling endosomes is required for autophagosome formation
Autor: | Kenta Imai, Yasuhiro Tsuji, Yukako Oe, Feike Hao, Yasuhiro Araki, Takeshi Noda, Naonobu Fujita, Maho Hamasaki, Tamotsu Yoshimori |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Autophagosome Endosome Protein subunit Amino Acid Motifs Adaptor Protein Complex 2 Vesicular Transport Proteins Autophagy-Related Proteins Endosomes Biology Models Biological 03 medical and health sciences symbols.namesake Structure-Activity Relationship Salmonella Autophagy Animals Humans Mice Knockout Autophagosomes Signal transducing adaptor protein Membrane Proteins Cell Biology Golgi apparatus Transmembrane protein Endocytosis Cell biology Protein Transport 030104 developmental biology Cytoplasm Gene Knockdown Techniques symbols Tyrosine HeLa Cells trans-Golgi Network |
Zdroj: | Journal of cell science. 129(20) |
ISSN: | 1477-9137 |
Popis: | Autophagy is an intracellular degradation pathway conserved in eukaryote. Among core Autophagy-related (Atg) proteins, mammalian Atg9A is the sole multi-spanning transmembrane protein, and both of the N- and C-terminal domains are exposed to the cytoplasm. It is known that Atg9A travels through the trans-Golgi network (TGN) and the endosomal system under nutrient-rich conditions and transiently localizes to the autophagosome upon autophagy-induction. However, the significance of Atg9A trafficking in autophagosome formation remains elusive. Here we identified sorting motifs at the N-terminal cytosolic stretch of Atg9A, which interact with an adaptor protein, AP-2. Atg9A mutant at the sorting motifs could not execute autophagy and is abnormally accumulated at the recycling endosomes. These combinational defects in autophagy and the Atg9A traffic out of the recycling endosomes were also caused by the knock down of TRAPPC8, a specific subunit of the TRAPPIII complex. These results show directly that the trafficking of Atg9A through the recycling endosomes is an essential step for autophagosome formation. |
Databáze: | OpenAIRE |
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