Activity-Dependent Phosphorylation of GluR1/4 by PKA is Subunit Specific
Wilson, Christopher G.
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α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are ionotropic glutamate receptors that mediate fast excitatory responses in neurons. Receptors containing subunits GluR1 or GluR4 are involved in the initial response to synaptic activity, and are known to be phosphorylated by protein kinase A (PKA) at serine residue 845 and 842, respectively. Little is known about the biochemical pathways that lead to the phosphorylation of these residues by PKA, and it is even thought that CaMKII may play a role here as well. Through several experiments employing Western Blot analysis of rat hippocampal slices using phospho-specific antibodies, we have been able to determine how spontaneous synaptic activity affects this phosphorylation. The results show that synaptic activity does lead to the phosphorylation of GluR4 by PKA but does not regulate GluR1 phosphorylation. Additional results show that calcium-calmodulin dependent kinase II (CaMKII) has no affect on the phosphorylation of GluR1 at serine 845, and that the number of phosphorylated GluR1 and 4 subunits increases with age. It is then suspected that although the cell may use these subunits for similar purposes, the biochemical regulation of their delivery to synapses may be different. Such information provides greater insight to the question of how long-term potentiation (LTP) -- our best molecular model for learning and memory-functions in the brain.