Expressions of CCAAT/Enhancer-binding proteins beta and delta and their activities are intensified by cAMP signaling as well as Ca2+/calmodulin kinases activation in hippocampal neurons.
The transcription factor, Aplysia CCAAT enhancer-binding protein (ApC/EBP), plays a crucial role in long term facilitation, a synaptic mechanism of long term memory in Aplysia. To gain a clue to whether the mammalian C/EBP family of transcription factors are also involved in long term memory, we examined how C/EBP activities in hippocampal neurons can be modulated in response to cAMP and Ca2+, crucial inductive signals for memory formation. As a result, stimulation of either cAMP or Ca2+ signals in hippocampal neurons was found to enhance mRNA expressions and DNA binding activities of C/EBPbeta and C/EBPdelta. Furthermore, it is indicated that CaM kinases have essential roles for increasing the expression and DNA binding activities of C/EBPbeta in hippocampal neurons activated by membrane depolarization. Overexpression of constitutively active calcium/calmodulin-dependent kinase IV was found to directly stimulate either C/EBPbeta-dependent or C/EBPdelta-dependent transcription, reinforcing the evidence that C/EBP family members contribute to Ca2+-dependent transcription. Thus, these results suggest that C/EBPbeta and C/EBPdelta may be involved in the transcription-dependent phase of memory formation by increasing the expression of both the DNA binding and the transcriptional activities under the direction of cAMP and/or Ca2+ signaling in hippocampal neurons.
Yukawa
K
K
Department of Physiology II, Wakayama Medical College, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. yukawa@ragtime.biken.osaka-u.ac.jp
Tanaka
T
T
Tsuji
S
S
Akira
S
S
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction
D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases