Havekes, RobbertCanton, David APark, Alan JHuang, TedNie, TingDay, Jonathan PGuercio, Leonardo AGrimes, QuinnLuczak, Vincent GGelman, Irwin HBaillie, George S2023-05-222023-05-222012-12-022017-07-17https://repository.upenn.edu/handle/20.500.14332/2751A 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.Copyright © 2012 the authors 0270-6474/12/3218137-13$15.00/0Amino Acids, Peptides, and ProteinsMedical NeurobiologyNeurologyNeuroscience and NeurobiologyArticle