PXD010103-1

PXD010103 is an original dataset announced via ProteomeXchange.

Title	AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A
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 TGN 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.
HostingRepository	PRIDE
AnnounceDate	2018-09-27
AnnouncementXML	Submission_2018-09-27_07:06:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georg Borner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-12 03:52:59	ID requested
⏵ 1	2018-09-27 07:06:58	announced
2	2018-10-08 03:37:12	announced	Updated publication reference for PubMed record(s): 30262884.
3	2024-10-22 04:46:07	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: AP-4, autophagy, vesicles, human cells, Dynamic Organellar Maps

Georg H H Borner
contact affiliation	Max Planck Institute of Biochemistry Department of Proteomics and Signal Transduction Am Klopferspitz 18 82152 Martinsried, Germany
contact email	borner@biochem.mpg.de
lab head
Georg Borner
contact affiliation	Max Planck Institute of Biochemistry
contact email	borner@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010103
     1. Label: PRIDE project
     2. Name: AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A