Title:Interaction of Different Proteins with GABAA 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 (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.