ArticleThe Journal of biological chemistry2019
Lysosomal targeting of the ABC transporter TAPL is determined by membrane-localized charged residues.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Alternate MHC I Antigen Presentation Pathways Allow CD8+ T-cell Recognition and Killing of Cancer Cells in the Absence of β2M or TAP.Cancer immunology research · 2025Article
- Single-Cell RNA Sequencing Integrated with Bulk-RNA Sequencing Analysis Reveals Prognostic Signatures Based on PANoptosis in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- Cellular insights into transposable elements in Alzheimer's disease.Frontiers in molecular biosciences · 2025Article
- Interdomain communication in a homodimeric ABC transporter.The Journal of biological chemistry · 2024Article
- Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer.Biomedicines · 2024Review
- Identification of two novel heterodimeric ABC transporters in melanoma: ABCB5β/B6 and ABCB5β/B9.The Journal of biological chemistry · 2024Article
- The β Isoform of Human ATP-Binding Cassette B5 Transporter, ABCB5β, Localizes to the Endoplasmic Reticulum.International journal of molecular sciences · 2023Article
- Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review.Biomedicines · 2023Review
- The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase.Nature communications · 2022Article
- Expanding the mutational landscape and clinical phenotype of the YIF1B related brain disorder.Brain : a journal of neurology · 2021Article
- The First Cytoplasmic Loop in the Core Structure of the ABCC1 (Multidrug Resistance Protein 1; MRP1) Transporter Contains Multiple Amino Acids Essential for Its Expression.International journal of molecular sciences · 2021Article
- Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.Redox biology · 2021Article
- Article
- Prognostic and immune regulating roles of YIF1B in Pan-Cancer: a potential target for both survival and therapy response evaluation.Bioscience reports · 2020Article
- Peptide translocation by the lysosomal ABC transporter TAPL is regulated by coupling efficiency and activation energy.Scientific reports · 2019Article
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Authors and funding
11 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human lysosomal polypeptide ABC transporter TAPL (ABC subfamily B member 9, ABCB9) transports 6-59-amino-acid-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 a 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.