Journal article
Gravin Orchestrates Protein Kinase A and beta 2-Adrenergic Receptor Signaling Critical for Synaptic Plasticity and Memory
The Journal of neuroscience, Vol.32(50), pp.18137-18149
12/12/2012
DOI: 10.1523/JNEUROSCI.3612-12.2012
PMID: 23238728
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 beta 2-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 beta 2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal beta 2-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 beta 2-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.
Details
- Title: Subtitle
- Gravin Orchestrates Protein Kinase A and beta 2-Adrenergic Receptor Signaling Critical for Synaptic Plasticity and Memory
- Creators
- Robbert HavekesDavid A CantonAlan J ParkTed HuangTing NieJonathan P DayLeonardo A GuercioQuinn GrimesVincent LuczakIrwin H GelmanGeorge S BaillieJohn D ScottTed Abel - University of Iowa, Biochemistry and Molecular Biology
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.32(50), pp.18137-18149
- DOI
- 10.1523/JNEUROSCI.3612-12.2012
- PMID
- 23238728
- ISSN
- 1529-2401
- eISSN
- 1529-2401
- Language
- English
- Date published
- 12/12/2012
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984071747702771
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