PXD016190

PXD016190 is an original dataset announced via ProteomeXchange.

Title	PTPN23 is required for endocytic sorting of neurotrophin receptors via a BICD1- dependent mechanism
Description	Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors, tropomyosin receptor kinases (Trks) and p75NTR, have been characterised over the years, including formation of activated ligand-receptor complexes, their endocytosis, trafficking and signalling. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors to their final cellular destination are not completely understood. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of BDNF-activated TrkB and p75NTR in motor neurons. Here, we deciphered the mechanism responsible for this sorting process. Using a proteomic approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1 knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_12:31:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bram Snijders
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-07 08:31:25	ID requested
⏵ 1	2020-05-26 12:32:00	announced

Budzinska MI, Villarroel-Campos D, Golding M, Weston A, Collinson L, Snijders AP, Schiavo G, PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors. J Cell Sci, 133(6):(2020) [pubmed]

submitter keyword: GeLC-MS,MaxQuant,iBAQ,Interaction proteomics

Bram Snijders
contact affiliation	The Francis Crick Institute
contact email	bram.snijders@crick.ac.uk
lab head
Bram Snijders
contact affiliation	The Francis Crick Institute
contact email	bram.snijders@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016190
     1. Label: PRIDE project
     2. Name: PTPN23 is required for endocytic sorting of neurotrophin receptors via a BICD1- dependent mechanism