Molecular mechanisms underlying the regulation of AMPA-type glutamate receptor trafficking by its interacting proteins for synaptic plasticity and memory

Abstract

Dynamic trafficking of AMPA-type glutamate receptor (AMPA-R) in neuronal cells is a key cellular mechanism for learning and memory in the brain, which is regulated by AMPA-R interacting proteins. Although several postsynaptic proteins that interact with the AMPA-R have been identified as potential regulator of AMPA-R trafficking, the precise mechanism for the modulation of AMPA-R trafficking in and out of synapse is still under investigation. Here, we performed the precise functional study of LARGE, novel interactor of AMPA-R, revealed through our proteomic analysis. Also, we have identified Cav subunit that mediated the interaction between $Ca_v$ and AMPA-R, which can examine their functional association in postsynaptic membrane. Our functional study of LARGE, an intellectual disability-associated protein, indicates that the fine-tuning of AMPA-R trafficking by it as a molecule linking Hebbian and homeostatic synaptic plasticity, which is critical for memory stability is critical for memory formation in the brain. Next, The functional association of Cav2 with AMPA-type glutamate receptor (AMPA-R) in the postsynaptic membrane was mentioned in our previous study. Here, we have identified Cav subunit ($\alpha 1$) that mediates the interaction between Cav2 and AMPA-R through a series of biochemical experiments. which can increases the cell surface localization of AMPA-R. Altogether, our study identified molecular mechanisms underlying the regulation ofA MPA-type glutamate receptor trafficking by its interacting proteins for synaptic plasticity and memory.