The Role of Collybistin in Gephyrin Clustering at Inhibitory Synapses: Facts and Open Questions

Abstract

Collybistin (Cb) is a brain-specific GDP/GTP-exchange factor, which interacts with the inhibitory receptor anchoring protein gephyrin. Data from mice carrying an inactivated Cb gene indicate that Cb is required for the formation and maintenance of gephyrin and gephyrin-dependent GABA(A) receptor (GABA(A)R) clusters at inhibitory postsynapses in selected regions of the mammalian forebrain. However, important aspects of how Cb's GDP/GTP-exchange activity, structure, and regulation contribute to gephyrin and GABA(A)R clustering, as well as its role in synaptic plasticity, remain poorly understood. Here we review the current state of knowledge about Cb's function and address open questions concerning its contribution to synapse formation, maintenance, plasticity, and adaptive changes in response to altered network activity.