PXD011899

PXD011899 is an original dataset announced via ProteomeXchange.

Title	USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7
Description	The endosomal system is a highly dynamic multifunctional organelle, whose complexity is regulated in part by reversible ubiquitylation. Despite the wide-ranging influence of ubiquitin in endosomal processes, relatively few enzymes utilizing ubiquitin have been described to control endosome integrity and function. Here we reveal the deubiquitylating enzyme (DUB) ubiquitin-specific protease 32 (USP32) as a powerful new player in this context. Loss of USP32 inhibits late endosome (LE) transport and recycling of LE cargos to the TGN, resulting in dispersion and swelling of the late compartment. Using SILAC-based ubiquitome profiling we identify the small GTPase Rab7—the logistical centerpiece of LE biology—as a substrate of USP32. Mechanistic studies reveal that LE transport effector RILP prefers ubiquitylation-deficient Rab7, while retromer-mediated LE recycling benefits from an intact cycle of Rab7 ubiquitylation. Collectively, our observations suggest that reversible ubiquitylation helps switch Rab7 between its various functions, thereby maintaining global spatiotemporal order in the endosomal system.
HostingRepository	PRIDE
AnnounceDate	2019-03-20
AnnouncementXML	Submission_2019-04-03_04:36:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benedikt Kessler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-30 01:40:56	ID requested
1	2019-03-20 09:26:07	announced
⏵ 2	2019-04-03 04:36:21	announced	Updated publication reference for PubMed record(s): 30926795.

Sapmaz A, Berlin I, Bos E, Wijdeven RH, Janssen H, Konietzny R, Akkermans JJ, Erson-Bensan AE, Koning RI, Kessler BM, Neefjes J, Ovaa H, USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7. Nat Commun, 10(1):1454(2019) [pubmed]

curator keyword: Biological

submitter keyword: endosomal trafficking, ubiquitin, USP32, ubiquitin specific protease, Rab GTPase

Benedikt M Kessler
contact affiliation	Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Headington OX3 7FZ, United Kingdom
contact email	kesslerbenedikt@gmail.com
lab head
Benedikt Kessler
contact affiliation	University of Oxford
contact email	kesslerbenedikt@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011899
     1. Label: PRIDE project
     2. Name: USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7