Luminal heterodimeric amino acid transporter defective in cystinuria.
Mutations of the glycoprotein rBAT cause cystinuria type I, an autosomal recessive failure of dibasic amino acid transport (b(0,+) type) across luminal membranes of intestine and kidney cells. Here we identify the permease-like protein b(0,+)AT as the catalytic subunit that associates by a disulfide bond with rBAT to form a hetero-oligomeric b(0,+) amino acid transporter complex. We demonstrate its b(0,+)-type amino acid transport kinetics using a heterodimeric fusion construct and show its luminal brush border localization in kidney proximal tubule. These biochemical, transport, and localization characteristics as well as the chromosomal localization on 19q support the notion that the b(0,+)AT protein is the product of the gene defective in non-type I cystinuria.
Pfeiffer
R
R
Institute of Physiology, University of Zürich, CH-8057 Zürich, Switzerland.
Loffing
J
J
Rossier
G
G
Bauch
C
C
Meier
C
C
Eggermann
T
T
Loffing-Cueni
D
D
Kühn
L C
LC
Verrey
F
F
D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D003555:Cystinuria / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D016415:Sequence Alignment; D014982:Xenopus laevis
D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human; C499488:Slc7a9 protein, mouse