Functional genomics of epilepsy-associated mutations in the GABA_A receptor subunits reveal that one mutation impairs function and two are catastrophic.

ABSTRACT: A number of epilepsy-causing mutations have recently been identified in the genes of the α1, β3, and γ2 subunits comprising the γ-aminobutyric acid type A (GABA_A) receptor. These mutations are typically dominant, and in certain cases, such as the α1 and β3 subunits, they may lead to a mix of receptors at the cell surface that contain no mutant subunits, a single mutated subunit, or two mutated subunits. To determine the effects of mutations in a single subunit or in two subunits on receptor activation, we created a concatenated protein assembly that links all five subunits of the α1β3γ2 receptor and expresses them in the correct orientation. We created nine separate receptor variants with a single-mutant subunit and four receptors containing two subunits of the γ2^R323Q

SUBMITTER: Absalom NL 

PROVIDER: S-EPMC6463728 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature