ATG12–ATG3 interacts with Alix to promote basal autophagic flux and late endosome function
| Autor: | Jayanta Debnath, Ritu Malhotra, Lyndsay M. Murrow |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Endosome
Viral budding Green Fluorescent Proteins Molecular Sequence Data Autophagy-Related Proteins Endosomes Ubiquitin-conjugating enzyme Biology Article ESCRT ATG12 Mice 03 medical and health sciences 0302 clinical medicine Genes Reporter Calcium-binding protein Autophagy Animals Amino Acid Sequence Calcium Signaling Late endosome 030304 developmental biology 0303 health sciences Calcium-Binding Proteins Proteins Cell Biology Fibroblasts Cell biology Luminescent Proteins Gene Expression Regulation 030220 oncology & carcinogenesis Ubiquitin-Conjugating Enzymes Autophagy-Related Protein 12 Gene Deletion |
| Zdroj: | Debnath, Jayanta; Murrow, L; & Malhotra, R. (2015). ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/7236b521 Nature cell biology |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb3112 |
| Popis: | The ubiquitin-like molecule ATG12 is required for the early steps of autophagy. Recently, we identified ATG3, the E2-like enzyme required for LC3 lipidation during autophagy, as an ATG12 conjugation target. Here, we demonstrate that cells lacking ATG12-ATG3 have impaired basal autophagic flux, accumulation of perinuclear late endosomes, and impaired endolysosomal trafficking. Furthermore, we identify an interaction between ATG12-ATG3 and the ESCRT-associated protein Alix (also known as PDCD6IP) and demonstrate that ATG12-ATG3 controls multiple Alix-dependent processes including late endosome distribution, exosome biogenesis, and viral budding. Lastly, similar to ATG12-ATG3, Alix is functionally required for efficient basal, but not starvation-induced, autophagy. Overall, these results identify a link between the core autophagy and ESCRT machineries and uncover a role for ATG12-ATG3 in late endosome function that is distinct from the canonical role of either ATG in autophagosome formation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|