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| Subject Categories: Signal Transduction | Neuroscience |
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| The EMBO Journal
(2007) 26, 4879–4890, doi:10.1038/sj.emboj.7601884 Published online 1 November 2007 |
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| Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP |
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| Yuan Lu1, Margaret Allen2, Amy R Halt1, Michael Weisenhaus2, Robert F Dallapiazza1, Duane D Hall1, Yuriy M Usachev1, G Stanley McKnight2 and Johannes W Hell1 |
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1 Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA 2 Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA To whom correspondence should be addressed Johannes W Hell, Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, 2-512 BSB, 51 Newton Road, Iowa City, IA 52242-1109, USA. Tel.: +1 319 384 4732; Fax: +1 319 335 8930; E-mail: johannes-hell@uiowa.edu Received 21 February 2007; Accepted 19 September 2007; Published online 1 November 2007. |
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| Abstract |
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| Association of PKA with the AMPA receptor GluR1 subunit via the A kinase anchor protein AKAP150 is crucial for GluR1 phosphorylation. Mutating the AKAP150 gene to specifically prevent PKA binding reduced PKA within postsynaptic densities (>70%). It abolished hippocampal LTP in 7–12 but not 4-week-old mice. Inhibitors of PKA and of GluR2-lacking AMPA receptors blocked single tetanus LTP in hippocampal slices of 8 but not 4-week-old WT mice. Inhibitors of GluR2-lacking AMPA receptors also prevented LTP in 2 but not 3-week-old mice. Other studies demonstrate that GluR1 homomeric AMPA receptors are the main GluR2-lacking AMPA receptors in adult hippocampus and require PKA for their functional postsynaptic expression during potentiation. AKAP150-anchored PKA might thus critically contribute to LTP in adult hippocampus in part by phosphorylating GluR1 to foster postsynaptic accumulation of homomeric GluR1 AMPA receptors during initial LTP in 8-week-old mice. |
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| Keywords: AKAP, AMPA receptors, calcium, PKA, synapse |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSA thorny question: how does activity maintain dendritic spines? Nature Neuroscience News and Views (01 Jan 1999) RESEARCHAge-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP The EMBO Journal Article SK2 channel plasticity contributes to LTP at Schaffer collateral?CA1 synapses Nature Neuroscience Article (01 Feb 2008) |
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