PT  - JOURNAL ARTICLE
AU  - Robbert Havekes
AU  - David A. Canton
AU  - Alan J. Park
AU  - Ted Huang
AU  - Ting Nie
AU  - Jonathan P. Day
AU  - Leonardo A. Guercio
AU  - Quinn Grimes
AU  - Vincent Luczak
AU  - Irwin H. Gelman
AU  - George S. Baillie
AU  - John D. Scott
AU  - Ted Abel
TI  - Gravin Orchestrates Protein Kinase A and β2-Adrenergic Receptor Signaling Critical for Synaptic Plasticity and Memory
AID  - 10.1523/JNEUROSCI.3612-12.2012
DP  - 2012 Dec 12
TA  - The Journal of Neuroscience
PG  - 18137--18149
VI  - 32
IP  - 50
4099  - http://www.jneurosci.org/content/32/50/18137.short
4100  - http://www.jneurosci.org/content/32/50/18137.full
SO  - J. Neurosci.2012 Dec 12; 32
AB  - A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plasticity and memory storage. In the forebrain, the anchoring protein gravin recruits a signaling complex containing PKA, PKC, calmodulin, and PDE4D (phosphodiesterase 4D) to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including β2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal β2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK in the CA1 region of the hippocampus are attenuated in mice lacking gravin-α. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced β2-adrenergic receptor signaling and ERK activation in the hippocampus in vivo, thereby organizing molecular interactions between glutamatergic and noradrenergic signaling pathways for long-lasting synaptic plasticity, and memory storage.