Interaction of Different Proteins with GABA(A) Receptor and their Modulatory Effect on Inhibitory Neural Transmission Leads to Epilepsy

摘要

gamma-aminobutyric acid type A receptors (GABA(A)Rs) are key players in the mediation of synaptic inhibition in the mammalian brain. Several proteins have a significant role in the complex trafficking mechanisms of GABA(A)Rs to and from the neuronal surface. Proper trafficking maintain number and localization of GABA(A)R at the neuronal surface which is necessary for inhibitory neuronal transmission. Among many other proteins, recently identified molecular motor protein KIF5A is also involved in the GABA(A)R trafficking by interacting with GABARAP protein. Deletion in the KIF5A can impair transportation mechanism of GABA(A)R, while an inappropriate inhibitory GABA(A)R mediated neuronal transmission leads to epilepsy. In this article, we discussed the dynamic regulation of GABA(A)R, role of different proteins in GABA(A)R trafficking, clustering and endocytosis by direct interaction with GABA(A)R or interaction through adaptor proteins linked with microtubules and also the dysregulation of GABA(A)R trafficking in epilepsy. It is concluded that various proteins are involved in the GABA(A)R trafficking; mutation or any other change in the interacting proteins can reduce the GABA(A)R trafficking and also reduces their cell surface expression which may lead to epilepsy.