Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family

• Published in: The EMBO journal Vol. 18; no. 1; pp. 49 - 57
• Main Authors: Pfeiffer, Rahel, Rossier, Grégoire, Spindler, Benjamin, Meier, Christian, Kühn, Lukas, Verrey, François
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 04-01-1999; Blackwell Publishing Ltd
• Subjects: amino acid exchanger; Amino Acid Sequence; Amino Acid Transport Systems; Amino acids; Amino Acids - metabolism; Animals; Antigens, CD - chemistry; Antigens, CD - genetics; Antigens, CD - metabolism; Biological Transport, Active; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Dimerization; epithelial transport; Female; Fusion Regulatory Protein-1; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; In Vitro Techniques; lysinuric protein intolerance; Mice; Molecular Sequence Data; Oocytes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Tissue Distribution; Xenopus laevis; Xenopus oocytes
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.1.49

Amino acid transport across cellular membranes is mediated by multiple transporters with overlapping specificities. We recently have identified the vertebrate proteins which mediate Na+‐independent exchange of large neutral amino acids corresponding to transport system L. This transporter consists of a novel amino acid permease‐related protein (LAT1 or AmAT‐L‐lc) which for surface expression and function requires formation of disulfide‐linked heterodimers with the glycosylated heavy chain of the h4F2/CD98 surface antigen. We show that h4F2hc also associates with other mammalian light chains, e.g. y+LAT1 from mouse and human which are ∼48% identical with LAT1 and thus belong to the same family of glycoprotein‐associated amino acid transporters. The novel heterodimers form exchangers which mediate the cellular efflux of cationic amino acids and the Na+‐dependent uptake of large neutral amino acids. These transport characteristics and kinetic and pharmacological fingerprints identify them as y+L‐type transport systems. The mRNA encoding my+LAT1 is detectable in most adult tissues and expressed at high levels in kidney cortex and intestine. This suggests that the y+LAT1–4F2hc heterodimer, besides participating in amino acid uptake/secretion in many cell types, is the basolateral amino acid exchanger involved in transepithelial reabsorption of cationic amino acids; hence, its defect might be the cause of the human genetic disease lysinuric protein intolerance.