Havekes, R. et al. (2012) Gravin orchestrates protein kinase A and 2-adrenergic receptor signaling critical for synaptic plasticity and memory. Journal of Neuroscience, 32(50), pp. 18137-18149. (doi: 10.1523/JNEUROSCI.3612-12.2012)
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Publisher's URL: http://dx.doi.org/10.1523/JNEUROSCI.3612-12.2012
Abstract
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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Baillie, Professor George and Day, Dr Jonathan |
Authors: | Havekes, R., Canton, D.A., Park, A.J., Huang, T., Nie, T., Day, J.P., Guercio, L.A., Grimes, Q., Luczak, V., Gelman, I.H., Baillie, G.S., Scott, J.D., and Abel, T. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Journal of Neuroscience |
Publisher: | The Society for Neuroscience |
ISSN: | 0270-6474 |
ISSN (Online): | 1529-2401 |
Copyright Holders: | Copyright © 2012 The Authors |
First Published: | First published in Journal of Neuroscience 32(50):18137-18149 |
Publisher Policy: | Reproduced under a Creative Commons License |
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