AMPA-type Glutamate Receptor Trafficking in Neurons of the Hippocampus
Tamm, Brendan J.
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During changes in the stimulation and firing rates of a neuron, the cell alters the strengths of its synapses in order to maintain homeostatic firing rates. Lasting changes in the strengths of these synapses are thought to be the physical mechanism for learning and memory in the brain. Changes in synaptic strength are brought about by the trafficking of receptor proteins to and from the cell membrane at synapses, and resolving the mechanism by which this movement occurs is integral to understanding learning in the brain. Research has found that the complex containing the proteins PIKfyve, FIG4 and VAC14 is involved in receptor protein transport to and from the membrane. These proteins are known to mitigate phopshoinositide levels within the cell, which control a myriad of activities including endosomal determination. PIKfyve converts PI(3)P to PI(3,5)P2, which commits endocytosed vessicles to the endosomal pathway. In order to better understand the role of PIKfyve and its phosphoinositide product in receptor protein trafficking, this study pharmacologically inhibited PIKfyve and measured rates of exocytosis following NMDA stimulated endocytosis and fluorescent bleaching. No substantial difference was seen in the rates of exocytosis between the inhibited and control cells, leaving an unclear picture of the role of PIKfyve and PI(3,5)P2. Future studies may seek to study this mechanism using different approaches that more directly interact with PIKfyve.