Cloning, Expression Patterns, and Chromosome Localization of Three Human and Two Mouse Homologues of GABAA Receptor-Associated Protein

Abstract

Type A receptors of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, contain α, β, δ, γ, and ρ subunits. The γ subunit has four subtypes: γ1, γ2, γ3, andγ4. GABAA receptor-associated protein (GABARAP) was previously demonstrated to act as a linker protein between microtubules and the γ2 subunit of GABAA receptors. However, no other linker proteins have been identified as mediating the linkage of microtubules and the remaining subunits of GABAA receptors. In this study we identified three human paralogues (GABARAPL1, GABARAPL2, and GABARAPL3) and two mouse orthologues (Gabarapl1 and Gabarapl2) of human GABARAP, all of which encoded 117 amino acids, as does Gabarapl. The expression patterns of GABARAPL1, GABARAPL2, and GABARAP in 16 adult tissues showed that they were expressed ubiquitously. The expression levels of GABARAPL1 as a 2.3-kb transcript were very high in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle, very low in thymus and small intestine, and moderate in other tissues tested. The unique 1.35-kb transcript of GABARAPL2 was expressed at high levels in heart, brain, testis, prostate, ovary, spleen, and skeletal muscle, at very low levels in lung, thymus, and small intestine, and moderately in other tissues tested. For GABARAP, a 1.3-kb transcript was abundantly expressed in all tested tissues with small variation. The expression patterns of Gabarapl1 and Gabarapl2 were similar to those of their counterparts in human. In addition, GABARAPL1 was localized to human chromosome 12p12.3 and GABARAPL2 to 16q22.3–q24.1 by RH mapping, while GABARAP and GABARAPL3 were found to be localized at chromosomes 17p13.2 and 15q25.1, respectively, by searching the related databases. Sequence comparison of the cDNAs and their corresponding genomic sequences shows that GABARAP, GABARAPL1, and GABARAPL2 are composed of four exons each, while GABARAPL3 is distributed only at one exon.