Gravin orchestrates protein kinase A and β2-adrenergic receptor signaling critical for synaptic plasticity and memory.

A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target 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 calmodulin, and PDE4D (phosphodiesterase 4D) to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in 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 duanyu1529, 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 duanyu1529 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.

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