LAT1 takes part in the transport of a wide range of neutral amino acids, especially ones with large branched or aromatic side chains. While transport carried out by either chain alone is negligible, the heavy chain is only needed to stabilize the dimer and facilitate its translocation to the plasma membrane, and the actual transport is carried out by the light chain. LAT1 heterodimerizes with the 4F2hc (SLC3A2) heavy chain, an N-glycosylated ~68-kDa transmembrane protein with 1 membrane-spanning domain. The LAT1 holotransporter consists of a 55-kDa light chain, SCL7A5 (LAT1 proper), and an escort protein called the heavy chain covalently linked to the light chain via a disulfide bond. Like all members of the heteromeric amino acid transporter (HAT, SLC7) family, LAT1 resides in the plasma membrane in a heterodimeric form. įunction, physiology, and clinically significant polymorphisms However, CD98 is even more broadly expressed since it works as an escort protein for other SLC7 members as well. The expression of CD98 correlates with that of SLC7A5 in terms of localization, as expected from the interaction between the two proteins. Īccording to the Human Protein Atlas, mRNA coding for the heavy chain CD98 is ubiquitously detected, with the highest expression level in kidney, placenta, testis and bone marrow. In the placenta, LAT1 is present on both the maternal and fetal surfaces of the syncytiotrophoblast. In other polarized epithelia, it is mainly localized in basolateral membranes. In the blood-brain barrier, LAT1 is localized on both the apical and basolateral membranes. LAT1 is ubiquitously expressed, with highest levels observed in the brain, spleen, bone marrow, testis, and placenta. Despite its known role in drug transport, the current regulatory guidelines contain no recommendation on investigating interactions of NCEs with LAT1. LAT1 also transports thyroid hormones, and it is the major importer of amino acid-like CNS drugs across the BBB. Therefore, LAT1 and the glutamine-preferring amino acid exchanger ASCT2 are thought to be functionally coupled in some cancer types. Although some controversy exists whether LAT1 carries out uniport or antiport activity, it is generally modelled as an obligatory exchanger that imports neutral amino acids, including some essential ones such as leucine and tryptophan, in exchange for intracellular nonessential amino acids, mainly glutamine. LAT1 preferentially transports large branched and aromatic neutral amino acids, mostly to proliferating cells and through barriers like the placenta and the blood-brain barrier (BBB). Its dimerization partner, 4F2hc (SLC3A2) heavy chain, is indispensable for its translocation to the plasma membrane and stability but not for the intrinsic transport function. the leucine-preferring group of amino acid transporters. ‘L-type’ in its traditional name refers to its classification with ‘System L’, i.e. LAT1 is a heterodimeric, sodium- and pH-independent amino acid transporter. Gene name: solute carrier family 7 member 5 (SLC7A5) LAT1 (L-type / large neutral amino acid transporter 1)Īliases: SLC7A5, 4F2lc, CD98lc, D16S469E, E16, MPE16 arrow_forwardOatp2b1 - cynomolgus monkey.arrow_forwardOatp1b3 -cynomolgus monkey.arrow_forwardOatp1b1 - cynomolgus monkey.
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