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 4F 2hc (genes SLC3A1 and SLC3A2, respectively, in the nomenclature of the Huma n Genome Organization) were identified as putative heavy subunits of mammal ian amino acid transporters. In 1994, it was demonstrated that mutations in SLC3A1 cause type I cystinuria. Very recently, several light subunits of t he heteromeric amino acid transporters have been identified. In 1999, a put ative light subunit of rBAT (the SLC7A9 gene; complementary DNA and protein termed b(o,+)AT) and a light subunit of 4F2hc (the SLC7A7 gene; cDNA and p rotein termed y(+)LAT-1) were shown to be the non-type I cystinuria and lys inuric protein intolerance genes, respectively. In this review, the charact eristics of these heteromeric amino acid transporters and their role in the se inherited aminoacidurias is described. Curr Opin Nephrol Hypertens 9:547 -553. (C) 2000 Lippincott Williams & Wilkins.