Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters

Abstract

Molecular biology entered the field of mammalian amino acid transporters in 1990-1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 20 mammalian amino acid transporters. All of them belong to four protein families. Here we describe the tissue expression, transport characteristics, structure-function relationship, and the putative physiological roles of these transporters. Wherever possible, the ascription of these transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of amino acid transport in mammals in the last 3 years, such as the construction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing number of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene (rBAT) responsible for an inherited disease of amino acid transport (cystinuria) has been identified. Identifying the molecular structure of amino acid transport systems of high physiological relevance (e.g., system A, L, N, and x(c)- and of the genes responsible for other aminoacidurias as well as revealing the key molecular mechanisms of the amino acid transporters are the main challenges of the future in this field.

δ-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is mediated by beta transporters

“…BETA transporters are GAT-1 to GAT-3, BGT-1 and TAUT (Palacín et al, 1998). We have observed that betaine, the substrate of BGT-1, has no effect on ALA uptake and neither has methyl-AIB, an inhibitor of TAUT system (Palacín et al, 1998). Consequently, GAT-1 to GAT-3, the high-affinity GABA transporters, seem to be the best candidates for ALA transport in our murine mammary adenocarcinoma cell system.…”

“…Moreover, in our cell system ALA incorporation appears not to be mediated either by the amino acid transport systems A, ASC, GLY, IMINO, PHE and B8 because the substrates for these transporters, that is methyl-aminoisobutyrate (alfa-Me-AIB), alanine, glycine, proline and phenylalanine (Palacín et al, 1998) do not significantly affect ALA incorporation. ALA methyl ester does not inhibit ALA uptake, in agreement with Rud et al (2000) and Gederaas et al (2001), who reported that ALA and its derivative ALA methyl ester, do not share the same transport system.…”

“…ALA incorporation is strongly inhibited by GABA and the b-amino acids, b-alanine and taurine, while betaine has no effect. GABA and b-amino acids are substrates of BETA trans- porters (Palacín et al, 1998). Nipecotic acid, an inhibitor of GABA transporters (GAT-1 to GAT-3), diminishes ALA uptake by 50%, whereas the ALA derivative methyl-ALA (Me-ALA) does not.…”

“…Other authors suggested that BETA transporters are involved in ALA transport (Rud et al, 2000). The BETA transporter family comprises GAT-1 to GAT-3, BGT-1 and TAUT transport systems (Palacín et al, 1998).…”

Relationship between [ 14 C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [ 3 H]methionine uptake

“…Therefore, natural or artificial amino acid analogs have been widely studied clinically as potential post-FDG radiopharmaceuticals for PET imaging; One of the most important radiolabeled amino acids in this regard is [S-methyl-11 C]-L-methionine ([ 11 C]MET) [6,7]. Since both amino acid transport and protein synthesis rates are enhanced in tumors, [ 11 [8,9].…”