Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2015 Mar 01;5935:1273-89. doi: 10.1113/jphysiol.2014.283960.
Show Gene links
Show Anatomy links
Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development.
Guetg A, Mariotta L, Bock L, Herzog B, Fingerhut R, Camargo SM, Verrey F.
???displayArticle.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, kidneyproximal 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.
Ando,
Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice.
2011, Pubmed
Ando,
Impairment of peripheral circadian clocks precedes metabolic abnormalities in ob/ob mice.
2011,
Pubmed Babu,
Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters.
2003,
Pubmed
,
Xenbase Back,
Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor.
2013,
Pubmed Bandsma,
Mechanisms behind decreased endogenous glucose production in malnourished children.
2010,
Pubmed Bisgaard,
Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1.
2002,
Pubmed Bodoy,
Identification of LAT4, a novel amino acid transporter with system L activity.
2005,
Pubmed
,
Xenbase Borsani,
SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance.
1999,
Pubmed Braun,
Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8.
2011,
Pubmed Bröer,
The role of amino acid transporters in inherited and acquired diseases.
2011,
Pubmed Camargo,
Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations.
2009,
Pubmed
,
Xenbase Cheval,
Atlas of gene expression in the mouse kidney: new features of glomerular parietal cells.
2011,
Pubmed Cleal,
Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast.
2011,
Pubmed Costa,
Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children.
1999,
Pubmed Dai,
Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects.
2002,
Pubmed Danilczyk,
Essential role for collectrin in renal amino acid transport.
2006,
Pubmed
,
Xenbase Dave,
Expression of heteromeric amino acid transporters along the murine intestine.
2004,
Pubmed Dudek,
Decreased translation of Dio3 mRNA is associated with drug-induced hepatotoxicity.
2013,
Pubmed Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase Fickert,
Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.
2001,
Pubmed Fukuhara,
Protein characterization of NA+-independent system L amino acid transporter 3 in mice: a potential role in supply of branched-chain amino acids under nutrient starvation.
2007,
Pubmed
,
Xenbase Glaudemans,
A primary culture system of mouse thick ascending limb cells with preserved function and uromodulin processing.
2014,
Pubmed Gridley,
Comparison of proton and electron radiation effects on biological responses in liver, spleen and blood.
2011,
Pubmed Heisterkamp,
The human gamma-glutamyltransferase gene family.
2008,
Pubmed Hsieh,
Protein profilings in mouse liver regeneration after partial hepatectomy using iTRAQ technology.
2009,
Pubmed Hunt,
The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism.
2002,
Pubmed Huq,
Changes in serum amino acid concentrations during prolonged endurance running.
1993,
Pubmed Ji,
Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.
1987,
Pubmed Kaplan,
Apical localization of the Na-K-Cl cotransporter, rBSC1, on rat thick ascending limbs.
1996,
Pubmed Loffing,
Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman's syndrome.
2004,
Pubmed Makrides,
Transport of amino acids in the kidney.
2014,
Pubmed Mariotta,
T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control.
2012,
Pubmed Massa,
Liver glucokinase: An overview on the regulatory mechanisms of its activity.
2011,
Pubmed Meier,
Activation of system L heterodimeric amino acid exchangers by intracellular substrates.
2002,
Pubmed
,
Xenbase Moret,
Regulation of renal amino acid transporters during metabolic acidosis.
2007,
Pubmed Nässl,
The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet.
2011,
Pubmed Poncet,
The role of amino acid transporters in nutrition.
2013,
Pubmed Postic,
Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice.
2008,
Pubmed Ramadan,
Recycling of aromatic amino acids via TAT1 allows efflux of neutral amino acids via LAT2-4F2hc exchanger.
2007,
Pubmed
,
Xenbase Ramadan,
Basolateral aromatic amino acid transporter TAT1 (Slc16a10) functions as an efflux pathway.
2006,
Pubmed
,
Xenbase Rudnick,
The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction.
2014,
Pubmed Shigeoka,
Suppression of nonsense-mediated mRNA decay permits unbiased gene trapping in mouse embryonic stem cells.
2005,
Pubmed Sipowicz,
Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected with Helicobacter hepaticus.
1997,
Pubmed Soll,
Serotonin promotes tumor growth in human hepatocellular cancer.
2010,
Pubmed Sperandeo,
Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance.
2007,
Pubmed Spoelstra,
Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic β-cell dysfunction.
2012,
Pubmed Sterchi,
Meprins, membrane-bound and secreted astacin metalloproteinases.
2008,
Pubmed Taylor,
Accumulation of free amino acids in growing Xenopus laevis oocytes.
1987,
Pubmed
,
Xenbase Verrey,
Kidney amino acid transport.
2009,
Pubmed Wagner,
Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins.
2008,
Pubmed Wiktor-Jedrzejczak,
Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse.
1990,
Pubmed Wolfsdorf,
Hypoalaninemia and ketotic hypoglycemia: cause or consequence?
1982,
Pubmed Xie,
Lack of the alanine-serine-cysteine transporter 1 causes tremors, seizures, and early postnatal death in mice.
2005,
Pubmed
