Gravin orchestrates protein kinase A and 2-adrenergic receptor signaling critical for synaptic plasticity and memory

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
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 > Institute of Cardiovascular and Medical Sciences
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438301Phosphodiesterase-4 isoforms - intracellular targeting, regulation and potential therapeutic targetsMiles HouslayMedical Research Council (MRC)G0600765RI NEUROSCIENCE & PSYCHOLOGY
432501Transatlantic networks of excellence in cardiovascular diseaseGeorge BaillieFoundation Leducq (LEDUCQ-VIL)06 CVD 02RI NEUROSCIENCE & PSYCHOLOGY