FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2523379436> ?p ?o ?g. }

• W2523379436 endingPage "20461" @default.
• W2523379436 startingPage "20440" @default.
• W2523379436 abstract "The subunit stoichiometry and arrangement of synaptic αβγ GABAA receptors are generally accepted as 2α:2β:1γ with a β-α-γ-β-α counterclockwise configuration, respectively. Whether extrasynaptic αβδ receptors adopt the analogous β-α-δ-β-α subunit configuration remains controversial. Using flow cytometry, we evaluated expression levels of human recombinant γ2 and δ subunits when co-transfected with α1 and/or β2 subunits in HEK293T cells. Nearly identical patterns of γ2 and δ subunit expression were observed as follows: both required co-transfection with α1 and β2 subunits for maximal expression; both were incorporated into receptors primarily at the expense of β2 subunits; and both yielded similar FRET profiles when probed for subunit adjacency, suggesting similar underlying subunit arrangements. However, because of a slower rate of δ subunit degradation, 10-fold less δ subunit cDNA was required to recapitulate γ2 subunit expression patterns and to eliminate the functional signature of α1β2 receptors. Interestingly, titrating γ2 or δ subunit cDNA levels progressively altered GABA-evoked currents, revealing more than one kinetic profile for both αβγ and αβδ receptors. This raised the possibility of alternative receptor isoforms, a hypothesis confirmed using concatameric constructs for αβγ receptors. Taken together, our results suggest a limited cohort of alternative subunit arrangements in addition to canonical β-α-γ/δ-β-α receptors, including β-α-γ/δ-α-α receptors at lower levels of γ2/δ expression and β-α-γ/δ-α-γ/δ receptors at higher levels of expression. These findings provide important insight into the role of GABAA receptor subunit under- or overexpression in disease states such as genetic epilepsies. The subunit stoichiometry and arrangement of synaptic αβγ GABAA receptors are generally accepted as 2α:2β:1γ with a β-α-γ-β-α counterclockwise configuration, respectively. Whether extrasynaptic αβδ receptors adopt the analogous β-α-δ-β-α subunit configuration remains controversial. Using flow cytometry, we evaluated expression levels of human recombinant γ2 and δ subunits when co-transfected with α1 and/or β2 subunits in HEK293T cells. Nearly identical patterns of γ2 and δ subunit expression were observed as follows: both required co-transfection with α1 and β2 subunits for maximal expression; both were incorporated into receptors primarily at the expense of β2 subunits; and both yielded similar FRET profiles when probed for subunit adjacency, suggesting similar underlying subunit arrangements. However, because of a slower rate of δ subunit degradation, 10-fold less δ subunit cDNA was required to recapitulate γ2 subunit expression patterns and to eliminate the functional signature of α1β2 receptors. Interestingly, titrating γ2 or δ subunit cDNA levels progressively altered GABA-evoked currents, revealing more than one kinetic profile for both αβγ and αβδ receptors. This raised the possibility of alternative receptor isoforms, a hypothesis confirmed using concatameric constructs for αβγ receptors. Taken together, our results suggest a limited cohort of alternative subunit arrangements in addition to canonical β-α-γ/δ-β-α receptors, including β-α-γ/δ-α-α receptors at lower levels of γ2/δ expression and β-α-γ/δ-α-γ/δ receptors at higher levels of expression. These findings provide important insight into the role of GABAA receptor subunit under- or overexpression in disease states such as genetic epilepsies." @default.
• W2523379436 created "2016-09-30" @default.
• W2523379436 creator A5021794918 @default.
• W2523379436 creator A5026219637 @default.
• W2523379436 creator A5027556015 @default.
• W2523379436 creator A5044198884 @default.
• W2523379436 creator A5048772790 @default.
• W2523379436 creator A5050564949 @default.
• W2523379436 creator A5086476295 @default.
• W2523379436 date "2016-09-01" @default.
• W2523379436 modified "2023-10-18" @default.
• W2523379436 title "Comparison of γ-Aminobutyric Acid, Type A (GABAA), Receptor αβγ and αβδ Expression Using Flow Cytometry and Electrophysiology" @default.
• W2523379436 cites W1482497049 @default.
• W2523379436 cites W1490270569 @default.
• W2523379436 cites W1490295882 @default.
• W2523379436 cites W1499228887 @default.
• W2523379436 cites W1575801138 @default.
• W2523379436 cites W1592243888 @default.
• W2523379436 cites W1598454484 @default.
• W2523379436 cites W1684501056 @default.
• W2523379436 cites W1739145755 @default.
• W2523379436 cites W1798308120 @default.
• W2523379436 cites W1948082071 @default.
• W2523379436 cites W1966456749 @default.
• W2523379436 cites W1967891742 @default.
• W2523379436 cites W1968479246 @default.
• W2523379436 cites W1969283272 @default.
• W2523379436 cites W1973238622 @default.
• W2523379436 cites W1982371070 @default.
• W2523379436 cites W1988139687 @default.
• W2523379436 cites W1989108188 @default.
• W2523379436 cites W1991847312 @default.
• W2523379436 cites W1999501054 @default.
• W2523379436 cites W2011620653 @default.
• W2523379436 cites W2013596724 @default.
• W2523379436 cites W2015236121 @default.
• W2523379436 cites W2016321438 @default.
• W2523379436 cites W2029072580 @default.
• W2523379436 cites W2029215893 @default.
• W2523379436 cites W2047243202 @default.
• W2523379436 cites W2061267746 @default.
• W2523379436 cites W2064354423 @default.
• W2523379436 cites W2064487331 @default.
• W2523379436 cites W2068375642 @default.
• W2523379436 cites W2073637383 @default.
• W2523379436 cites W2075961210 @default.
• W2523379436 cites W2077060302 @default.
• W2523379436 cites W2077065023 @default.
• W2523379436 cites W2077386756 @default.
• W2523379436 cites W2078051444 @default.
• W2523379436 cites W2082956738 @default.
• W2523379436 cites W2094581263 @default.
• W2523379436 cites W2095238547 @default.
• W2523379436 cites W2105758845 @default.
• W2523379436 cites W2110725469 @default.
• W2523379436 cites W2113281208 @default.
• W2523379436 cites W2128736659 @default.
• W2523379436 cites W2128843823 @default.
• W2523379436 cites W2131995085 @default.
• W2523379436 cites W2133458388 @default.
• W2523379436 cites W2137471600 @default.
• W2523379436 cites W2152236836 @default.
• W2523379436 cites W2154128645 @default.
• W2523379436 cites W2313915838 @default.
• W2523379436 cites W3022203673 @default.
• W2523379436 doi "https://doi.org/10.1074/jbc.m115.698860" @default.
• W2523379436 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5034041" @default.
• W2523379436 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27493204" @default.
• W2523379436 hasPublicationYear "2016" @default.
• W2523379436 type Work @default.
• W2523379436 sameAs 2523379436 @default.
• W2523379436 citedByCount "23" @default.
• W2523379436 countsByYear W25233794362016 @default.
• W2523379436 countsByYear W25233794362017 @default.
• W2523379436 countsByYear W25233794362018 @default.
• W2523379436 countsByYear W25233794362019 @default.
• W2523379436 countsByYear W25233794362020 @default.
• W2523379436 countsByYear W25233794362021 @default.
• W2523379436 countsByYear W25233794362022 @default.
• W2523379436 countsByYear W25233794362023 @default.
• W2523379436 crossrefType "journal-article" @default.
• W2523379436 hasAuthorship W2523379436A5021794918 @default.
• W2523379436 hasAuthorship W2523379436A5026219637 @default.
• W2523379436 hasAuthorship W2523379436A5027556015 @default.
• W2523379436 hasAuthorship W2523379436A5044198884 @default.
• W2523379436 hasAuthorship W2523379436A5048772790 @default.
• W2523379436 hasAuthorship W2523379436A5050564949 @default.
• W2523379436 hasAuthorship W2523379436A5086476295 @default.
• W2523379436 hasBestOaLocation W25233794361 @default.
• W2523379436 hasConcept C104292427 @default.
• W2523379436 hasConcept C104317684 @default.
• W2523379436 hasConcept C153911025 @default.
• W2523379436 hasConcept C164083038 @default.
• W2523379436 hasConcept C168258287 @default.
• W2523379436 hasConcept C170493617 @default.
• W2523379436 hasConcept C188987157 @default.
• W2523379436 hasConcept C190472901 @default.
• W2523379436 hasConcept C19876734 @default.

• next