Collybistingephyrin

Collybistingephyrin is the functional complex formed by the interaction of collybistin and gephyrin, two proteins essential for organizing inhibitory synapses in the vertebrate brain. Collybistin, encoded by the ARHGEF9 gene, is a neuron-specific guanine nucleotide exchange factor that activates small GTPases and contributes to the targeting of gephyrin to postsynaptic sites. Gephyrin is a cytosolic scaffold protein that anchors GABA_A receptors and glycine receptors at inhibitory synapses. Through their interaction, collybistin promotes the assembly and stabilization of gephyrin-containing receptor clusters at postsynaptic membranes, thereby facilitating inhibitory synaptic transmission.

The complex is dynamically regulated during development and synaptic plasticity and is influenced by signaling pathways that regulate cytoskeletal organization and receptor trafficking. Mutations in ARHGEF9 or disruptions of the collybistin-gephyrin interaction can impair inhibitory synapse formation and function, and have been linked to X-linked intellectual disability and epilepsy in humans, among other neurological disorders. Research on collybistin-gephyrin continues to elucidate mechanisms of synaptic organization, the structural basis for receptor clustering, and how alterations in this complex contribute to disease.

The study of this complex also informs broader understanding of inhibitory circuitry and its role in neural network stability and information processing.