Differential mechanisms of glutamate receptor regulation of SynGAP in cortical neurones.
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/alpha-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 Ca2+, 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.
Rockliffe
Nichola
N
The Physiological laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. nichola.rockliffe@liverpool.ac.uk
Gawler
Debra
D
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D011905:Genes, ras / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000076122:Disks Large Homolog 4 Protein; D018690:Excitatory Amino Acid Agonists; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007555:Isoxazoles; D007608:Kainic Acid; D008565:Membrane Proteins; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C501449:Dlg4 protein, rat; C121001:NR2B NMDA receptor; C112202:Syngap1 protein, rat; C418233:2-amino-3-(3-hydrox-5(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl)propionic acid