Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Yuan Lu; Margaret Allen; Amy R Halt; Michael Weisenhaus; Robert F Dallapiazza; Duane D Hall; Yuriy M Usachev; G Stanley McKnight; Johannes W Hell

doi:10.1038/sj.emboj.7601884

Back

Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Journal article

Open access

Peer reviewed

Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP

Yuan Lu, Margaret Allen, Amy R Halt, Michael Weisenhaus, Robert F Dallapiazza, Duane D Hall, Yuriy M Usachev, G Stanley McKnight and Johannes W Hell

The EMBO journal, Vol.26(23), pp.4879-4890

11/28/2007

DOI: 10.1038/sj.emboj.7601884

PMCID: PMC2099463

PMID: 17972919

Files and links (1)

url

https://europepmc.org/articles/pmc2099463View

Published (Version of record) Open Access

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.

calcium

AMPA receptors

synapse

AKAP

PKA

Details

Title: Subtitle: Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP
Creators: Yuan Lu - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Margaret Allen - Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA
Amy R Halt - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Michael Weisenhaus - Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA
Robert F Dallapiazza - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Duane D Hall - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Yuriy M Usachev - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
G Stanley McKnight - Department of Pharmacology, School of Medicine, University of Washington, Seattle, WA, USA
Johannes W Hell - Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: The EMBO journal, Vol.26(23), pp.4879-4890
DOI: 10.1038/sj.emboj.7601884
PMID: 17972919
PMCID: PMC2099463
NLM abbreviation: EMBO J
ISSN: 0261-4189
eISSN: 1460-2075
Publisher: Nature Publishing Group
Alternative title: LTP requirement of PKA and GluR2-lacking AMPARs
Language: English
Date published: 11/28/2007
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984070863002771

Metrics

29 Record Views

149 Times Cited - Web of Science