Science, Vol.276, No.5321, 2042-2045, 1997
Regulatory Phosphorylation of Ampa-Type Glutamate Receptors by CAM-Kii During Long-Term Potentiation
Longterm 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.
Keywords:DEPENDENT PROTEIN-KINASE;II MUTANT MICE;HIPPOCAMPAL-NEURONS;SYNAPTIC RESPONSES;ALPHA-SUBUNIT;RAT-BRAIN;LTP;MECHANISM;MODULATION;INHIBITOR