LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
Glycoprotein-associated amino acid transporters (gpaAT) are permease-related proteins that require heterodimerization to express their function. So far, four vertebrate gpaATs have been shown to associate with 4F2hc/CD98 for functional expression, whereas one gpaAT specifically associates with rBAT. In this study, we characterized a novel gpaAT, LAT2, for which mouse and human cDNAs were identified by expressed sequence tag data base searches. The encoded ortholog proteins are 531 and 535 amino acids long and 92% identical. They share 52 and 48% residues with the gpaATs LAT1 and y(+)LAT1, respectively. When mouse LAT2 and human 4F2hc cRNAs were co-injected into Xenopus oocytes, disulfide-linked heterodimers were formed, and an L-type amino acid uptake was induced, which differed slightly from that produced by LAT1-4F2hc: the apparent affinity for L-phenylalanine was higher, and L-alanine was transported at physiological concentrations. In the presence of an external amino acid substrate, LAT2-4F2hc also mediated amino acid efflux. LAT2 mRNA is expressed mainly in kidney and intestine, whereas LAT1 mRNA is expressed widely. Immunofluorescence experiments showed colocalization of 4F2hc and LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. In conclusion, LAT2 forms with LAT1 a subfamily of L-type gpaATs. We propose that LAT1 is involved in cellular amino acid uptake, whereas LAT2 plays a role in epithelial amino acid (re)absorption.
Rossier
G
G
Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges s/Lausanne, Switzerland.
Meier
C
C
Bauch
C
C
Summa
V
V
Sordat
B
B
Verrey
F
F
Kühn
L C
LC
D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D027261:Fusion Regulatory Protein-1; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011233:Precipitin Tests; D014018:Tissue Distribution; D014981:Xenopus
D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D015703:Antigens, CD; D002352:Carrier Proteins; D018076:DNA, Complementary; D027261:Fusion Regulatory Protein-1; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human; C499488:Slc7a9 protein, mouse