| First Author | Lo WY | Year | 2014 |
| Journal | Neurochem Res | Volume | 39 |
| Issue | 6 | Pages | 1088-103 |
| PubMed ID | 24213971 | Mgi Jnum | J:310940 |
| Mgi Id | MGI:6762827 | Doi | 10.1007/s11064-013-1187-9 |
| Citation | Lo WY, et al. (2014) Co-expression of gamma2 subunits hinders processing of N-linked glycans attached to the N104 glycosylation sites of GABAA receptor beta2 subunits. Neurochem Res 39(6):1088-103 |
| abstractText | GABAA receptors, the major mediators of fast inhibitory neuronal transmission, are heteropentameric glycoproteins assembled from a panel of subunits, usually including alpha and beta subunits with or without a gamma2 subunit. The alpha1beta2gamma2 receptor is the most abundant GABAA receptor in brain. Co-expression of gamma2 with alpha1 and beta2 subunits causes conformational changes, increases GABAA receptor channel conductance, and prolongs channel open times. We reported previously that glycosylation of the three beta2 subunit glycosylation sites, N32, N104 and N173, was important for alpha1beta2 receptor channel gating. Here, we examined the hypothesis that steric effects or conformational changes caused by gamma2 subunit co-expression alter the glycosylation of partnering beta2 subunits. We found that co-expression of gamma2 subunits hindered processing of beta2 subunit N104 N-glycans in HEK293T cells. This gamma2 subunit-dependent effect was strong enough that a decrease of gamma2 subunit expression in heterozygous GABRG2 knockout (gamma2(+/-)) mice led to appreciable changes in the endoglycosidase H digestion pattern of neuronal beta2 subunits. Interestingly, as measured by flow cytometry, gamma2 subunit surface levels were decreased by mutating each of the beta2 subunit glycosylation sites. The beta2 subunit mutation N104Q also decreased GABA potency to evoke macroscopic currents and reduced conductance, mean open time and open probability of single channel currents. Collectively, our data suggested that gamma2 subunits interacted with beta2 subunit N-glycans and/or subdomains containing the glycosylation sites, and that gamma2 subunit co-expression-dependent alterations in the processing of the beta2 subunit N104 N-glycans were involved in altering the function of surface GABAA receptors. |
