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Subcellular localization and endocytosis of homomeric γ2 subunit splice variants of γ-aminobutyric acid type A receptors

Connolly, CN; Uren, JM; Thomas, P; Gorrie, GH; Gibson, A; Smart, TG; Moss, SJ; (1999) Subcellular localization and endocytosis of homomeric γ2 subunit splice variants of γ-aminobutyric acid type A receptors. Molecular and Cellular Neurosciences , 13 (4) pp. 259-271. 10.1006/mcne.1999.0746.

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Abstract

The expression of α and β γ-aminobutyric acid type A receptor subunits produces GABA-gated channels which require the incorporation of either the γ2 or γ3 subunit for benzodiazepine modulation. Here we examine the role of the γ2 subunit splice variants, γ2S and γ2L which differ by eight amino acids in the major intracellular domain, in mediating cell surface expression. Using immunocytochemistry we have demonstrated that when expressed alone, the γ2S subunit can access the cell surface and internalize constitutively. In contrast, α1, β2 and γ2L are retained predominantly in the endoplasmic reticulum (ER) when expressed alone. Replacing the insert which differentiates γ2L from γ2S (LLRMFSFK) with eight alanines produces a phenotype identical to γ2S. Both γ2 subunits fail to produce high molecular weight oligomers observed for α1β2 and α1β2γ2 heterooligomers and do not form functional ion channels. Surface expression of γ2S is repressed upon the coexpression of α1 or β2 subunits, resulting in ER-retained heterooligomers, suggesting that homomeric γ2S is unlikely to occur in vivo. However, its independent maturation to surface competence and preferential assembly with α and β subunits may ensure the production of functional benzodiazepine-sensitive receptors. Furthermore, the presence of the γ2 subunit appears to confer an endocytotic capacity to these heterooligomeric receptors.

Type: Article
Title: Subcellular localization and endocytosis of homomeric γ2 subunit splice variants of γ-aminobutyric acid type A receptors
DOI: 10.1006/mcne.1999.0746
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/10025600
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