| Title: |
AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A. |
| Authors: |
Davies, AK; Itzhak, DN; Edgar, JR; Archuleta, TL; Hirst, J; Jackson, LP; Robinson, MS; Borner, GHH |
| Source: |
Davies, AK, Itzhak, DN, Edgar, JR, Archuleta, TL, Hirst, J, Jackson, LP, Robinson, MS & Borner, GHH 2018, 'AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A.', Nature Communications. https://doi.org/10.1038/s41467-018-06172-7 |
| Publication Year: |
2018 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Description: |
Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including ‘Dynamic Organellar Maps’, to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2. We demonstrate that AP-4 deficiency causes missorting of ATG9A in diverse cell types, including patient-derived cells, as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the trans-Golgi network to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the “ATG9A reservoir” required for autophagosome biogenesis. Our study uncovers ATG9A trafficking as a ubiquitous function of the AP-4 pathway. Furthermore, it provides a potential molecular pathomechanism of AP-4 deficiency, through dysregulated spatial control of autophagy. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/30262884; info:eu-repo/semantics/altIdentifier/pissn/2041-1723; info:eu-repo/semantics/altIdentifier/eissn/2041-1723 |
| DOI: |
10.1038/s41467-018-06172-7 |
| Availability: |
https://research.manchester.ac.uk/en/publications/966d7b05-6bdc-4a63-8fa0-bee7cf28d586; https://doi.org/10.1038/s41467-018-06172-7; http://europepmc.org/abstract/med/30262884 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.2E043876 |
| Database: |
BASE |