A recent study published in the Annals of the National Academy of Sciences (PNAS) investigated the crucial role of the Gephyrin protein in the formation of GABAergic synapses, which are essential for inhibitory neurotransmission in the nervous system. Using stem cell-derived human neurons and the CRISPR-Cas9 gene-editing tool, researchers at Colorado State University demonstrated that Gephyrin is critical for the autonomous assembly and synaptic localization of postsynaptic components, even in the absence of presynaptic GABA release.
This finding challenges previous knowledge about synapse formation, which was believed to be dependent on neuronal communication. The research also revealed that the deletion of Gephyrin or the Collybistin protein, associated with Gephyrin, significantly impaired the formation and positioning of synapses. In addition, Gephyrin-GABAAR clusters, formed without the presence of GABA, could be subsequently activated and even potentiated by the late release of GABA.
These findings provide valuable insight into the molecular mechanisms of synapse formation and open up new perspectives for the development of therapies for neurological disorders such as epilepsy, autism and schizophrenia, which are associated with mutations in the Gephyrin protein. By better understanding how Gephyrin influences brain connectivity, scientists can identify therapeutic targets and develop interventions to correct synaptic dysfunction and potentially prevent or treat these debilitating conditions.
Referência:
Chanda, S., et al. (2024). Gephyrin promotes autonomous assembly and synaptic localization of GABAergic postsynaptic components without presynaptic GABA release. Proceedings of the National Academy of Sciences (PNAS).
