Autophosphorylated calcium/calmodulin-dependent protein kinase II alpha induced by cerebral ischemia immediately targets and phosphorylates N-methyl-D-aspartate receptor subunit 2B (NR2B) in hippocampus of rats.
In this article, we investigated the autophosphorylation and translocation of calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha) in hippocampus during global ischemia. The following results were observed: (1) CaMKII alpha immediately became autophosphorylated after 3 min ischemia, at the same time, there is a dramatic and sustained translocation of CaMKII alpha from cytosolic fraction to synaptic fraction; (2) CaMKII alpha translocated to post-synaptic density and targeted N-methyl-D-aspartate receptor subunit 2B (NR2B) which was serine-phosphorylated by active CaMKII alpha; (3) serine phosphorylation of NR2B could not only inhibit the formation of CaMKII alpha-NR2B complexes but also promote the dissociation of the preformed complexes when ischemic time was prolonged. These results suggest that phosphorylation of NR2B can influence the channel properties of NR2B, and the dissociation of the CaMKII alpha-NR2B complexes may be a negative feedback mechanism during longer time cerebral ischemia.
Meng
Fanjie
F
Research Center of Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou 221002, Jiangsu, People's Republic of China.
Zhang
Guangyi
G
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat