Article
- The EMBO Journal (2007) 26, 4879 - 4890
- doi:10.1038/sj.emboj.7601884
Published online: 1 November 2007
Subject Categories:
Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP
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
- Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA
Correspondence to:
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
Abstract
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.
Keywords:
- AKAP,
- AMPA receptors,
- calcium,
- PKA,
- synapse
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