Developmental seizures and mortality result from reducing GABA_A receptor α2-subunit interaction with collybistin.

ABSTRACT: Fast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABA_ARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABA_ARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents. Gabra2-1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. Surviving Gabra2-1 m

SUBMITTER: Hines RM 

PROVIDER: S-EPMC6081406 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature