| First Author | Havekes R | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 50 | Pages | 18137-49 |
| PubMed ID | 23238728 | Mgi Jnum | J:192016 |
| Mgi Id | MGI:5463820 | Doi | 10.1523/JNEUROSCI.3612-12.2012 |
| Citation | Havekes R, et al. (2012) Gravin orchestrates protein kinase A and beta2-adrenergic receptor signaling critical for synaptic plasticity and memory. J Neurosci 32(50):18137-49 |
| abstractText | 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 beta2-adrenergic receptor. Here, we show that mice lacking the alpha-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including beta2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal beta2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK in the CA1 region of the hippocampus are attenuated in mice lacking gravin-alpha. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced beta2-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. |
