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
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability
Oncogene Review
NEWS AND VIEWS
A thorny question: how does activity maintain dendritic spines?
Nature Neuroscience News and Views (01 Jan 1999)
Delivering the goods to synapses
Nature Neuroscience News and Views (01 Nov 2000)
RESEARCH
SK2 channel plasticity contributes to LTP at Schaffer collateral?CA1 synapses
Nature Neuroscience Article (01 Feb 2008)
Nature Neuroscience Article (01 Sep 2003)
