System L: heteromeric exchangers of large, neutral amino acids involved in directional transport.
The plasma membrane transport system L is in many cells the only (efficient) pathway for the import of large branched and aromatic neutral amino acids. The corresponding transporters are hetero(di)mers composed of a catalytic subunit (LAT1 or LAT2=light chain=glycoprotein-associated amino acid transporter) associated covalently with the glycoprotein 4F2hc/CD98 (heavy chain). The tissue distribution of LAT1 suggests that it is involved mainly in transporting amino acids into growing cells and across some endothelial/epithelial secretory barriers, whereas the localization of LAT2 indicates that it is mainly involved in the basolateral efflux step of transepithelial (re)absorptive amino acid transport. However, system L transporters are obligatory amino acid exchangers with 1:1 stoichiometry, with similar (but not identical) intra- and extracellular substrate selectivities and with highly asymmetrical apparent affinities (low affinity inside). Therefore, net directional transport of large, neutral amino acids by system L depends on the parallel expression of a unidirectional transporter with overlapping selectivity (for instance systems A or N) that provides/recycles amino acids that drive system L exchange function. By mediating the regulated flux of these exchange substrates, unidirectional transporters control the activity of system L.
Verrey
François
F
University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057 Zürich, Switzerland. verrey@access.unizh.ch
D027062:Amino Acid Transport System L / Q000737:chemistry / Q000502:physiology*; D027182:Amino Acid Transport System y+; D021542:Amino Acids, Neutral / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004848:Epithelium / Q000378:metabolism; D027301:Fusion Regulatory Protein 1, Light Chains / Q000032:analysis / Q000378:metabolism; D027261:Fusion Regulatory Protein-1 / Q000032:analysis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000032:analysis / Q000378:metabolism; D009994:Osmolar Concentration; D014018:Tissue Distribution
D027062:Amino Acid Transport System L; D027182:Amino Acid Transport System y+; D021542:Amino Acids, Neutral; D027301:Fusion Regulatory Protein 1, Light Chains; D027261:Fusion Regulatory Protein-1; D027283:Large Neutral Amino Acid-Transporter 1; C420646:SLC7A8 protein, human