Alpha-isoform of Ca2+/calmodulin-dependent kinase II autophosphorylation is required for memory consolidation-specific transcription.
Autophosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II switches the kinase into an autonomous activity mode. This molecular switch is important for hippocampal long-term memory formation, which requires de novo gene transcription and protein synthesis. Here, we have studied whether auto-phosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II is required for gene transcription induced in the hippocampus by contextual fear conditioning. We have shown that upregulation of a nonassociative transcript, the serum and glucocorticoid-induced kinase-1 messenger RNA, is normal in alpha-isoform of Ca2+/calmodulin-dependent kinase II autophosphorylation-deficient mutant mice, whereas upregulation of an associative transcript, the nerve growth factor-inducible gene B messenger RNA, is impaired. Thus, we suggest that autophosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II is a biochemical switch that regulates association-specific consolidation processes.
von Hertzen
Laura S J
LS
Wolfson Institute for Biomedical Research, University College London, London, UK.
Giese
K Peter
KP
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000172:deficiency / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics; D005239:Fear; D005260:Female; D006624:Hippocampus / Q000502:physiology; D017874:Immediate-Early Proteins / Q000097:blood / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010766:Phosphorylation; D020033:Protein Isoforms / Q000172:deficiency / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000235:genetics; D011987:Receptors, Steroid / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000097:blood / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C539818:Nr4a1 protein, mouse