PXD010989

PXD010989 is an original dataset announced via ProteomeXchange.

Title	TAPL interaction network
Description	The human lysosomal polypeptide ABC transporter TAPL (ABC subfamily B member 9, ABCB9) transports 6–59 amino-acids-long polypeptides from the cytosol into lysosomes. The subcellular localization of TAPL depends solely on its N-terminal transmembrane domain TMD0, which lacks conventional targeting sequences. However, the intracellular route and the molecular mechanisms that control TAPL localization remain unclear. Here, we delineated the route of TAPL to lysosomes and investigated the determinants of single trafficking steps. By synchronizing trafficking events by retention using selective hooks (RUSH) assay and visualizing individual intermediate steps through immunostaining and confocal microscopy, we demonstrate that TAPL takes the direct route to lysosomes. We further identified conserved charged residues within TMD0 transmembrane helices that are essential for individual steps of lysosomal targeting. Substitutions of these residues retained TAPL in the endoplasmic reticulum (ER) or Golgi. We also observed that for release from the ER, a salt bridge between Asp-17 and Arg-57 is essential. An interactome analysis revealed that Yip1-interacting factor homolog B, membrane-trafficking protein (YIF1B) interacts with TAPL. We also found that YIF1B is involved in ER-to-Golgi trafficking and interacts with TMD0 of TAPL via its transmembrane domain and that this interaction strongly depends on the newly identified salt bridge within TMD0. These results expand our knowledge about lysosomal trafficking of TAPL and the general function of extra transmembrane domains of ABC transporters.
HostingRepository	PRIDE
AnnounceDate	2019-03-14
AnnouncementXML	Submission_2019-03-21_09:48:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Jung
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-03 03:41:28	ID requested
1	2019-03-14 08:05:02	announced
⏵ 2	2019-03-21 09:48:11	announced	Updated publication reference for PubMed record(s): 30877195.

Graab P, Bock C, Weiss K, Hirth A, Koller N, Braner M, Jung J, Loehr F, Tamp, é R, Behrends C, Abele R, Lysosomal targeting of the ABC transporter TAPL is determined by membrane-localized charged residues. J Biol Chem, 294(18):7308-7323(2019) [pubmed]

curator keyword: Biological

submitter keyword: LC-MS

Christian Behrends
contact affiliation	Munich Cluster for Systems Neurology, Ludwig-Maximilians-University, Feodor-Lynen Str. 17, 81377 München
contact email	Christian.Behrends@mail03.med.uni-muenchen.de
lab head
Jennifer Jung
contact affiliation	Scientist
contact email	jenneyjung@gmx.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/03/PXD010989

PRIDE project URI

• PRIDE
  1. PXD010989
     1. Label: PRIDE project
     2. Name: TAPL interaction network