The Journal of Neuroscience, September 28, 2005, 25(39):9037-9045; doi:10.1523/JNEUROSCI.1989-05.2005
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Cellular/Molecular
An Aplysia Type 4 Phosphodiesterase Homolog Localizes at the Presynaptic Terminals of Aplysia Neuron and Regulates Synaptic Facilitation
Hyungju Park,
Jin-A Lee,
Changhoon Lee,
Min-Jeong Kim,
Deok-Jin Chang,
Hyoung Kim,
Seung-Hee Lee,
Yong-Seok Lee, and
Bong-Kiun Kaang
National Research Laboratory of Neurobiology, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea
The cAMP-dependent signaling pathway is critically involved in memory-related synaptic plasticity. cAMP-specific type 4 phosphodiesterases (PDE4) play a role in this process by regulating the cAMP concentration. However, it is unclear how PDE4 is involved in regulating synaptic plasticity. To address this issue in Aplysia sensory-to-motor synapses, we identified a long isoform of the PDE4 homolog in Aplysia kurodai (apPDE), with genetic and biochemical properties similar to those of mammalian PDE4s. Furthermore, apPDE is localized to the membrane and presynaptic region. Both apPDE overexpression and knock-down impaired short- and long-term facilitation, indicating that an appropriate expression level of apPDE in synaptic regions is required for normal synaptic facilitation. By using fluorescence resonance energy transfer-based measurement of in vivo protein kinase A (PKA) activation, we found that the PKA activation by 5-hydroxytryptamine (5-HT) was impaired in both apPDE-overexpressed and knock-down synapses. Analogous to the inhibition of apPDE by RNA interference, chronic rolipram treatment before 5-HT stimulation also impaired the PKA activation by 5-HT, suggesting that regulation of the synaptic cAMP level by PDE4 is critical for normal synaptic facilitation. Together, we suggest that PDE4s localized in the synapses play a critical role in regulating the optimum cAMP level required for normal synaptic plasticity.
Key words: PDE4; cAMP; rolipram; synaptic facilitation; FRET; memory
Received May 17, 2005;
revised August 6, 2005;
accepted August 23, 2005.
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Y.-S. Lee, S.-L. Choi, S.-H. Lee, H. Kim, H. Park, N. Lee, S.-H. Lee, Y.-S. Chae, D.-J. Jang, E. R. Kandel, et al.
Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia
PNAS,
August 25, 2009;
106(34):
14634 - 14639.
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