ArticleScientific reports2019
Ubiquitylation and endocytosis of the human LAT1/SLC7A5 amino acid transporter.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- The Legionella pneumophila type IVb secretion system effector BinA subverts amino acid transport to sensitize TORC1 signaling in macrophages.PLoS pathogens · 2026Article
- Potential targets for boron transport in boron neutron capture therapy.Frontiers in oncology · 2026Review
- Commentary: LAT1 expression in head and neck cancer: a prognostic biomarker with potential relevance for BNCT.Frontiers in oncology · 2026Article
- TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.The EMBO journal · 2025Article
- Targeting Surface Markers in Anaplastic Thyroid Cancer: Future Directions in Ligand-bound Therapy.Journal of the Endocrine Society · 2025Review
- NEDD4 enhances bone‑tendon healing in rotator cuff tears by reducing fatty infiltration.Molecular medicine reports · 2025Article
- Structural basis of anticancer drug recognition and amino acid transport by LAT1.Nature communications · 2025Article
- TLR7: A Key Prognostic Biomarker and Immunotherapeutic Target in Lung Adenocarcinoma.Biomedicines · 2025Article
- Mechanistic Insight into Serine Flux Regulation through Nanoscale Organization of Glucose and Serine Transporters by Substrate Probe-Based Direct Stochastic Optical Reconstruction Microscopy Imaging.Research (Washington, D.C.) · 2025Article
- l-Type amino acid transporter 1-targeting nanoparticles for antisense oligonucleotide delivery to the CNS.Molecular therapy. Nucleic acids · 2024Article
- Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Article
- Targeting Transporters for Drug Delivery to the Brain: Can We Do Better?Pharmaceutical research · 2022Review
- Decrease of Intracellular Glutamine by STF-62247 Results in the Accumulation of Lipid Droplets in von Hippel-Lindau Deficient Cells.Frontiers in oncology · 2022Article
- Comparison of Experimental Strategies to Study l-Type Amino Acid Transporter 1 (LAT1) Utilization by Ligands.Molecules (Basel, Switzerland) · 2021Article
- Synthesis and Characterization of the Ethylene-Carbonate-Linked L-Valine Derivatives of 4,4-Dimethylcurcumin with Potential Anticancer Activities.Molecules (Basel, Switzerland) · 2021Article
- Protein kinase C activation upregulates human L-type amino acid transporter 2 function.The journal of physiological sciences : JPS · 2021Article
- Targeting SLC1A5 and SLC3A2/SLC7A5 as a Potential Strategy to Strengthen Anti-Tumor Immunity in the Tumor Microenvironment.Frontiers in immunology · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human L-type amino acid transporter 1 (LAT1), also known as SLC7A5, catalyzes the transport of large neutral amino acids across the plasma membrane. As the main transporter of several essential amino acids, notably leucine, LAT1 plays an important role in mTORC1 activation. Furthermore, it is overexpressed in various types of cancer cells, where it contributes importantly to sustained growth. Despite the importance of LAT1 in normal and tumor cells, little is known about the mechanisms that might control its activity, for example by promoting its downregulation via endocytosis. Here we report that in HeLa cells, activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) triggers efficient endocytosis and degradation of LAT1. Under these conditions we found LAT1 downregulation to correlate with increased LAT1 ubiquitylation. This modification was considerably reduced in cells depleted of the Nedd4-2 ubiquitin ligase. By systematically mutagenizing the residues of the LAT1 cytosolic tails, we identified a group of three close lysines (K19, K25, K30) in the N-terminal tail that are important for PMA-induced ubiquitylation and downregulation. Our study thus unravels a mechanism of induced endocytosis of LAT1 elicited by Nedd4-2-mediated ubiquitylation of the transporter's N-terminal tail.
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