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Cloning and Expression of a Betaine/GABA Transporter from Human Brain
Author(s) -
Borden Laurence A.,
Smith Kelli E.,
Gustafson Eric L.,
Branchek Theresa A.,
Weinshank Richard L.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64030977.x
Subject(s) - transporter , biology , betaine , neurotransmitter transporter , gaba transporter , amino acid , complementary dna , biochemistry , cdna library , northern blot , microbiology and biotechnology , gene
A cDNA clone encoding a human γ‐aminobutyric acid (GABA) transporter has been isolated from a brain cDNA library, and its functional properties have been examined in mammalian cells. The nucleotide sequence predicts a transporter with 614 amino acids and 12 putative transmembrane domains. The highest degree of amino acid identity is with a betaine/GABA transporter originally cloned from the dog termed BGT‐1 (91%) and a related transporter from mouse brain (87%). These identities are similar to those for species homologues of other neurotransmitter transporters and suggest that the new clone represents the human homologue of BGT‐1. The transporter displays high affinity for GABA (IC 50 of 30 µ M ) and is also sensitive to phloretin, l ‐2,4‐diaminobutyric acid, and hypotaurine (IC 50 values of ∼150–400 µ M ). The osmolyte betaine is ∼25‐fold weaker than GABA, displaying an IC 50 of ∼1 m M . The relative potencies of these inhibitors at human BGT‐1 differ from those of mouse and dog BGT‐1. Northern blot analysis reveals that BGT‐1 mRNA is widely distributed throughout the human brain. The cloning of the human homologue of BGT‐1 will further our understanding of the roles of GABA and betaine in neural function.