Collybistin SH3?protein isoforms are expressed in the rat brain promoting gephyrin and GABA?A receptor clustering at GABAergic synapses

Collybistin (CB) is a guanine nucleotide exchange factor (GEF) selectively localized at GABAergic and glycinergic postsynapses. Analysis of mRNA shows that several isoforms collybistin are expressed in the brain. Some have SH3 domain (CBSH3+) some no (CBSH3?). The CBSH3+ mRNAs predominantly over CBSH3?. However, an immunoblot study mouse brain homogenates, only protein were detected, proposing CBSH3? might not be expression or lack important issue because has strong effect promoting postsynaptic clustering gephyrin GABA-A receptors (GABAARs). Moreover constitutively active; therefore lower play relatively stronger functional role than more abundant but self-inhibited isoforms, which need to activated. We now showing that: (a) brain; (b) parvalbumin positive (PV+) interneurons show higher other neurons; (c) associated with synapses various regions (d) knocking down hippocampal neurons decreases synaptic GABAARs. results it plays significant size regulation postsynapse.