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Published 11 September 2006. doi:10.1083/jcb.200512066
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 6, 827-838
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Article

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



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 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.

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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