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Antisense suppression of GABA A receptor β subunit levels in cultured cerebellar granule neurons demonstrates their importance in receptor expression
Author(s) -
Kumar Mallika,
Luo Xiang,
Quirk Phillip L.,
Siegel Ruth E.
Publication year - 2001
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.1471-4159.2001.00217.x
Subject(s) - protein subunit , biology , receptor , interleukin 10 receptor, alpha subunit , gabaa rho receptor , messenger rna , gene isoform , microbiology and biotechnology , interleukin 5 receptor alpha subunit , gamma aminobutyric acid receptor subunit alpha 1 , granule cell , immunocytochemistry , gabaa receptor , biochemistry , g alpha subunit , central nervous system , neuroscience , endocrinology , gene , dentate gyrus
GABA A receptors in the CNS are pentameric molecules composed of α, β, γ, δ, ε and θ subunits. Studies on transfected cells have shown that GABA A receptor β subunit isoforms can direct α1 subunit localization within the cell. To examine the role of selected subunits in governing GABA A receptor expression in neurons, cultures of rat cerebellar granule cells were grown with antisense or sense oligodeoxynucleotides (ODNs) specific for the α1, β2 or γ2 subunits. These subunits are all expressed in granule neurons where they are thought to contribute to an abundant receptor type. Following ODN treatment, subunit expression and distribution were examined by western blotting, immunocytochemistry and RT‐PCR. Treatment of the cultures with the antisense, but not the corresponding sense, ODNs reduced the levels of the targeted subunit polypeptides. In addition, the β2 antisense ODN reduced the level of the α1 subunit polypeptide without altering the level of its mRNA. In contrast, treatment with the β2 subunit antisense ODN did not alter γ2 subunit polypeptide expression, distribution or mRNA level. These findings suggest that the α1 subunit requires a β subunit for assembly into GABA A receptors in cerebellar granule neurons.