Phosphorylation of hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during contextual fear conditioning: interactions between Erk-1/2 and Elk-1.
The phosphorylation of proteins involved in the MAP kinase signal transduction pathway was investigated during associative learning of C57BL/6J mice. Context-dependent fear conditioning, consisting of a single exposure of mice to a context followed by foot shock, was employed as a learning paradigm. Control groups consisted of mice exposed to context only or an immediate shock in the context. Coincident up-regulation of phosphorylated Erk-1/2 and Elk-1 was observed in the CA3 hippocampal subfield and dentate gyrus 30 min after fear conditioning but not after the control paradigms. Phosphorylated Erk-1/2 and Elk-1 were associated and predominantly colocalized in the mossy fibers. In vitro kinase assays showed that hippocampal Erk-1/2 phosphorylates Elk-1. Notably, Elk-1 in turn enhances the phosphorylation of Erk-1/2 and its downstream target p90Rsk-1. Increased phosphorylation and nuclear translocation of p90Rsk-1 was also demonstrated in the CA3 hippocampal area in vivo during contextual fear conditioning. The observed interactions between hippocampal Elk-1 and Erk-1/2 proteins may affect the consolidation of contextual memories through activation of the downstream nuclear targets of Erk-1/2, such as p90Rsk-1, without requiring nuclear translocation of Elk-1 and Erk-1/2.
Sananbenesi
Farahnaz
F
Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075, Goettingen, Germany.
Fischer
André
A
Schrick
Christina
C
Spiess
Joachim
J
Radulovic
Jelena
J
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003213:Conditioning, Psychological / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D014157:Transcription Factors; D015854:Up-Regulation / Q000502:physiology; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C016957:adenosine-3',5'-cyclic phosphorothioate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases