Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.
Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.
Barria
A
A
Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA.
Muller
D
D
Derkach
V
V
Griffith
L C
LC
Soderling
T R
TR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D010449:Peptide Mapping; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C063302:KN 62