Differential mechanisms of glutamate receptor regulation of SynGAP in cortical neurones.

Abstract One prime candidate linking N -methyl- d -aspartate (NMDA) receptors to the regulation of the MAP kinase cascade is SynGAP, a negative regulator of Ras. In order to assess how a physiological stimulus can alter SynGAP activity, an appropriate whole cell system must be used and SynGAP must be specifically extracted from membranes whilst preserving the catalytic activity of the protein. Here, we have achieved this and studied the effect of NMDA/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor stimulations on SynGAP activity in cortical neurones. Furthermore, we have examined the role of extracellular Ca 2+ , CaM kinase II and the PSD-95-NR2B subunit interaction in SynGAP activity regulation and propose a novel convergence of signalling between AMPA, kainate and NMDA receptors.