Heteromeric amino acid transporters explain inherited aminoacidurias.
In the past 5 years, the first genes responsible for aminoacidurias caused by defects in renal reabsorption transport mechanisms have been identified. These diseases are type I and non-type I cystinuria and lysinuric protein intolerance. This knowledge came from the molecular characterization of the first heteromeric amino acid transporters in mammals. In 1992, rBAT and 4F2hc (genes SLC3A1 and SLC3A2, respectively, in the nomenclature of the Human Genome Organization) were identified as putative heavy subunits of mammalian amino acid transporters. In 1994, it was demonstrated that mutations in SLC3A1 cause type I cystinuria. Very recently, several light subunits of the heteromeric amino acid transporters have been identified. In 1999, a putative light subunit of rBAT (the SLC7A9 gene; complementary DNA and protein termed amino acid transporter) and a light subunit of 4F2hc (the SLC7A7 gene; cDNA and protein termed y+LAT-1) were shown to be the non-type I cystinuria and lysinuric protein intolerance genes, respectively. In this review, the characteristics of these heteromeric amino acid transporters and their role in these inherited aminoacidurias is described.
Palacín
M
M
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Spain. mpalacin@porthos.bio.ub.es
Bertran
J
J
Zorzano
A
A
D020157:Amino Acid Transport Disorders, Inborn / Q000235:genetics* / Q000652:urine*; D000596:Amino Acids / Q000652:urine*; D003555:Cystinuria / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism
D000596:Amino Acids; D008239:Lysine