PSD-95 promotes CaMKII-catalyzed serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP after transient brain ischemia in rat hippocampus.
Recent studies have indicated that cerebral ischemia induces rapid serine phosphorylation of synaptic RAS-GTPase activating protein (SynGAP) by calcium/Camodulin-dependent protein kinase II (CaMKII) in rat hippocampus. To further illustrate the mechanisms underlying these processes, we examined the effects of transient (15 min) brain ischemia followed by reperfusion (0, 30 min, 6 h, 1, 3 days) on serine phosphorylation of SynGAP and interactions involving SynGAP, postsynaptic density protein 95 (PSD95) and CaMKII in rat hippocampus. Transient brain ischemia was induced by the method of four-vessel occlusion in Sprague-Dawley rats. Serine phosphorylation of SynGAP increased immediately after brain ischemia and peaked at 30-min reperfusion, and the increase was maintained for 3 days. The association among SynGAP, PSD95 and CaMKII had a similar trend as serine phosphorylation of SynGAP. Intracrebroventricular infusion of PSD95 antisense oligodeoxynucleotide not only markedly decreased the protein levels of PSD95 but also attenuated the elevated serine phosphorylation of SynGAP and the associations among SynGAP, PSD95 and CaMKII induced by 30-min reperfusion following 15-min brain ischemia. The results suggest that the serine phosphorylation of SynGAP catalyzed by CaMKII is immediately increased and that PSD95 is critical for promoting SynGAP serine phosphorylation after transient brain ischemia.
Song
Bo
B
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, PR China.
Yan
Xue-Bo
XB
Zhang
Guang-Yi
GY
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002384:Catalysis; D000076122:Disks Large Homolog 4 Protein; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C112202:Syngap1 protein, rat; C033652:postsynaptic density proteins; D012694:Serine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020559:Monomeric GTP-Binding Proteins