ArticleThe Journal of physiology2015
Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development.
Article in The Journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Genotypic and phenotypic consequences of domestication in dogs.G3 (Bethesda, Md.) · 2026Article
- Potential role of L-citrulline in regulating exercise performance and muscle protein metabolism.NPJ science of food · 2026Review
- Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1.The EMBO journal · 2026Article
- Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.Environment international · 2025Article
- Genotypic and phenotypic consequences of domestication in dogs.bioRxiv : the preprint server for biology · 2025Article
- Abundance of Amino Acid Transporters and mTOR Pathway Components in the Gastrointestinal Tract of Lactating Holstein Cows.Animals : an open access journal from MDPI · 2023Article
- Contribution of the L-Type Amino Acid Transporter Family in the Diagnosis and Treatment of Prostate Cancer.International journal of molecular sciences · 2023Review
- Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism.Biomolecules · 2022Article
- Dietary Enteromorpha polysaccharide-Zn supplementation regulates amino acid and fatty acid metabolism by improving the antioxidant activity in chicken.Journal of animal science and biotechnology · 2022Article
- Amino Acid Homeostasis in Mammalian Cells with a Focus on Amino Acid Transport.The Journal of nutrition · 2022Article
- Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations.Frontiers in endocrinology · 2022Article
- Molecular mechanism of nutrient uptake in developing embryos of oviparous cloudy catshark (Scyliorhinus torazame).PloS one · 2022Article
- Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, BJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Responsible Genes for Neuronal Migration in the Chromosome 17p13.3: BeyondBrain sciences · 2021Review
- Modulation of bioelectric cues in the evolution of flying fishes.Current biology : CB · 2021Article
- Expression of proposed methionine transporters along the gastrointestinal tract of pigs and their regulation by dietary methionine sources.Genes & nutrition · 2021Article
- Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use.Nutrients · 2021Review
- Effects of Dietary Valine Levels on Production Performance, Egg Quality, Antioxidant Capacity, Immunity, and Intestinal Amino Acid Absorption of Laying Hens during the Peak Lay Period.Animals : an open access journal from MDPI · 2021Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amino acid (AA) uniporter Lat4 (Slc43a2) mediates facilitated diffusion of branched-chain AAs, methionine and phenylalanine, although its physiological role and subcellular localization are not known. We report that Slc43a2 knockout mice were born at expected Mendelian frequency but displayed an ∼10% intrauterine growth retardation and low amniotic fluid AAs, suggesting defective transplacental transport. Postnatal growth was strongly reduced, with premature death occurring within 9 days such that further investigations were made within 3 days of birth. Lat4 immunofluorescence showed a strong basolateral signal in the small intestine, kidney proximal tubule and thick ascending limb epithelial cells of wild-type but not Slc43a2 null littermates and no signal in liver and skeletal muscle. Experiments using Xenopus laevis oocytes demonstrated that Lat4 functioned as a symmetrical low affinity uniporter with a K₀.₅ of ∼5 mm for both in- and efflux. Plasma AA concentration was decreased in Slc43a2 null pups, in particular that of non-essential AAs alanine, serine, histidine and proline. Together with an increased level of plasma long chain acylcarnitines and a strong alteration of liver gene expression, this indicates malnutrition. Attempts to rescue pups by decreasing the litter size or by nutrients injected i.p. did not succeed. Radioactively labelled leucine but not lysine given per os accumulated in the small intestine of Slc43a2null pups, suggesting the defective transcellular transport of Lat4 substrates. In summary, Lat4 is a symmetrical uniporter for neutral essential AAs localizing at the basolateral side of (re)absorbing epithelia and is necessary for early nutrition and development.
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