Published 11 September 2006. doi:10.1083/jcb.200512066
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 6, 827-838
PKA-activated ApAFApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation
Jin-A Lee1,
Sue-Hyun Lee1,
Changhoon Lee1,
Deok-Jin Chang1,
Yong Lee1,
Hyoung Kim1,
Ye-Hwang Cheang1,
Hyoung-Gon Ko1,
Yong-Seok Lee1,
Heejung Jun1,
Dusan Bartsch2,
Eric R. Kandel3, and
Bong-Kiun Kaang1
1 Institute of Molecular Biology and Genetics, RIO, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea
2 Department of Molecular Biology, Central Institute of Mental Health, J5, 68 159 Mannheim, Germany
3 Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Correspondence to Bong-Kiun Kaang: kaang{at}snu.ac.kr
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 ApAFApC/EBP heterodimer transactivates enhancer response elementcontaining genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAFApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF.
J.-A. Lee and S.-H. Lee contributed equally to this paper.
Abbreviations used in this paper: ANOVA, analysis of variance; ApAF, Aplysia activating factor; CRE, cAMP response element; ds, double stranded; EPSP, excitatory postsynaptic potential; ERE, enhancer response element; HT, hydroxytryptamine; LTF, long-term facilitation; PKA, protein kinase A; STF, short-term facilitation; WT, wild-type.

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