Interaction of Different Proteins with GABA_A Receptor and their Modulatory Effect on Inhibitory Neural Transmission Leads to Epilepsy

Title:Interaction of Different Proteins with GABA_A Receptor and their Modulatory Effect on Inhibitory Neural Transmission Leads to Epilepsy

Volume: 13 Issue: 7

Author(s): Muhammad Faheem, Adeel G. Chaudhary, Taha A. Kumosani, Mohammad H. Al-Qahtani, Muhammad Yasir, Fehmida Bibi, Myeong O. Kim, Mahmood Rasool and Muhammad I. Naseer

Affiliation:

Keywords: Epilepsy, temporal lobe epilepsy, γ-aminobutyric acid type A receptor, γ-aminobutyric acid type A receptor associated protein, molecular motor proteins, kinesin-1 family member protein.

Abstract: γ-aminobutyric acid type A receptors (GABA_ARs) 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_ARs to and from the neuronal surface. Proper trafficking maintain number and localization of GABA_AR 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_AR trafficking by interacting with GAB_ARP protein. Deletion in the KIF5A can impair transportation mechanism of GABA_AR, while an inappropriate inhibitory GABA_AR mediated neuronal transmission leads to epilepsy. In this article, we discussed the dynamic regulation of GABA_AR, role of different proteins in GABA_AR trafficking, clustering and endocytosis by direct interaction with GABA_AR or interaction through adaptor proteins linked with microtubules and also the dysregulation of GABA_AR trafficking in epilepsy. It is concluded that various proteins are involved in the GABA_AR trafficking; mutation or any other change in the interacting proteins can reduce the GABA_AR trafficking and also reduces their cell surface expression which may lead to epilepsy.

Cite this article as:

Faheem Muhammad, Chaudhary G. Adeel, Kumosani A. Taha, Al-Qahtani H. Mohammad, Yasir Muhammad, Bibi Fehmida, Kim O. Myeong, Rasool Mahmood and Naseer I. Muhammad, Interaction of Different Proteins with GABA_A Receptor and their Modulatory Effect on Inhibitory Neural Transmission Leads to Epilepsy, CNS & Neurological Disorders - Drug Targets 2014; 13 (7) . https://dx.doi.org/10.2174/1871527313666140917115121