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

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

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 13 , Issue 7 , 2014

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Abstract:

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

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.

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Article Details

VOLUME: 13
ISSUE: 7
Year: 2014
Page: [1148 - 1159]
Pages: 12
DOI: 10.2174/1871527313666140917115121
Price: $58

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