The function of neurogranin in the regulation of sodium channel and NMDA receptor channel

Abstract

Neurogranin (Ng), also known as RC3 and P17, is a postnatal expressed brain-specific protein that is selectively expressed high levels in neuronal cell bodies and dendrites. Ng contains a binding domain, IQ motif, for calmodulin (CaM). Recent studies have suggested that CaM directly interacts with both sodium channel and NMDA channel, and in turn regulates the channel kinetics. We report here that the intracellular infusion of a Ng peptide containing unphosphorylated IQ motif substantially modifies the functional properties of endogenous sodium channels in cortical neuron, while another control peptide containing a phosphorylated IQ motif does not. This result verifies that CaM plays a significant role in sodium channel signaling and suggests that the effect of Ng on sodium channel is through Ng-CaM complex. In contrast, both two Ng peptides have no specific effect on recombinant NMDA receptor channels expressed in HEK cells, suggesting apoCaM may pre-associate with the NR1 C0 region at resting.