Several posttranslational modifications act in concert to regulate gephyrin scaffolding and GABAergic transmission.

ABSTRACT: GABA_A receptors (GABA_ARs) mediate the majority of fast inhibitory neurotransmission in the brain via synergistic association with the postsynaptic scaffolding protein gephyrin and its interaction partners. However, unlike their counterparts at glutamatergic synapses, gephyrin and its binding partners lack canonical protein interaction motifs; hence, the molecular basis for gephyrin scaffolding has remained unclear. In this study, we identify and characterize two new posttranslational modifications of gephyrin, SUMOylation and acetylation. We demonstrate that crosstalk between SUMOylation, acetylation and phosphorylation pathways regulates gephyrin scaffolding. Pharmacological intervention of SUMO pathway or transgenic expression of SUMOylation-deficient gephyrin varia

SUBMITTER: Ghosh H 

PROVIDER: S-EPMC5103071 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature