MOLECULAR-BIOLOGY OF MAMMALIAN PLASMA-MEMBRANE AMINO-ACID TRANSPORTERS

Molecular biology entered the field of mammalian amino acid transporte rs in 1990-1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 2 0 mammalian amino acid transporters. All of them belong to four protei n families. Here we describe the tissue expression, transport characte ristics, structure-function relationship, and the putative physiologic al roles of these transporters. Wherever possible, the ascription of t hese transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of a mino acid transport in mammals in the last 3 years, such as the constr uction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing numbe r of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene (rBAT) respon sible for an inherited disease of amino acid transport (cystinuria) ha s been identified. Identifying the molecular structure of amino acid t ransport systems of high physiological relevance (e.g., system A, L, N , and x(c)(-)) and of the genes responsible for other aminoacidurias a s well as revealing the key molecular mechanisms of the amino acid tra nsporters are the main challenges of the future in this field.