PKA-activated ApAF-ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation.
Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF-ApC/EBP heterodimer transactivates enhancer response element-containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF-ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.
Lee
Jin-A
JA
Institute of Molecular Biology and Genetics, RIO, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
Lee
Sue-Hyun
SH
Lee
Changhoon
C
Chang
Deok-Jin
DJ
Lee
Yong
Y
Kim
Hyoung
H
Cheang
Ye-Hwang
YH
Ko
Hyoung-Gon
HG
Lee
Yong-Seok
YS
Jun
Heejung
H
Bartsch
Dusan
D
Kandel
Eric R
ER
Kaang
Bong-Kiun
BK
D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
C417672:ApAF protein, Aplysia; C097204:ApCREB2 protein, Aplysia californica; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases