Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory.
Because activation of ERK1/2 MAP kinase (MAPK) is critical for hippocampus-dependent memory, there is considerable interest in mechanisms for regulation of MAPK during memory formation. Here we report that MAPK and CREB-mediated transcription are negatively regulated by SCOP (suprachiasmatic nucleus [SCN] circadian oscillatory protein) and that SCOP is proteolyzed by calpain when hippocampal neurons are stimulated by brain-derived neurotrophic factor (BDNF), KCl depolarization, or NMDA. Moreover, training for novel object memory decreases SCOP in the hippocampus. To determine if hippocampus-dependent memory is influenced by SCOP in vivo, we generated a transgenic mouse strain for the inducible overexpression of SCOP in the forebrain. Overexpression of SCOP completely blocked memory for novel objects. We conclude that degradation of SCOP by calpain contributes to activation of MAPK during memory formation.
Shimizu
Kimiko
K
Department of Pharmacology, The University of Washington, Seattle, WA 98195, USA.
Phan
Trongha
T
Mansuy
Isabelle M
IM
Storm
Daniel R
DR
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018929:Cell Culture Techniques; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D050436:Regulatory Elements, Transcriptional; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D009687:Nuclear Proteins; D016202:N-Methylaspartate; D011189:Potassium Chloride; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D020928:Mitogen-Activated Protein Kinases; C519282:PHLPP1 protein, mouse; D010749:Phosphoprotein Phosphatases; D002154:Calpain; D002118:Calcium