Gephyrin: a central GABAergic synapse organizer

Gephyrin is a central element that anchors, clusters and stabilizes glycine and γ-aminobutyric acid type A receptors at inhibitory synapses of the mammalian brain. It self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins. Intriguingly, the clustering of gephyrin, which is regulated by multiple posttranslational modifications, is critical for inhibitory synapse formation and function. In this review, we summarize the basic properties of gephyrin and describe recent findings regarding its roles in inhibitory synapse formation, function and plasticity. We will also discuss the implications for the pathophysiology of brain disorders and raise the remaining open questions in this field. The formation and function of inhibitory synapses in the mammalian brain relies on a regulatory protein called gephyrin. In a review article, Gayoung Choii and Jaewon Ko from Yonsei University in Seoul, South Korea, discuss the roles of gephyrin in organizing the inhibitory synaptic structure that permits a nerve cell to pass on its signal to another cell. Gephyrin anchors and stabilizes receptors involved in inhibitory synaptic transmission between nerve cells. This allows for the propagation of the molecular messages involved in nerve cell inhibition. The authors discuss in detail how modifications to gephyrin affect how it builds scaffolds and thus how it interacts with other proteins. Gephyrin dysfunction has been linked to various neurological disorders, suggesting that it could be a suitable therapeutic target.