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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4879-4890 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 26 |
| Issue number | 23 |
| DOIs | |
| State | Published - Nov 28 2007 |
| Externally published | Yes |
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Keywords
- AKAP
- AMPA receptors
- Calcium
- PKA
- Synapse
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. / Lu, Yuan; Allen, Margaret; Halt, Amy R.; Weisenhaus, Michael; Dallapiazza, Robert F.; Hall, Duane D.; Usachev, Yuriy M.; McKnight, G. Stanley; Hell, Johannes W.
In: EMBO Journal, Vol. 26, No. 23, 28.11.2007, p. 4879-4890.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP
AU - Lu, Yuan
AU - Allen, Margaret
AU - Halt, Amy R.
AU - Weisenhaus, Michael
AU - Dallapiazza, Robert F.
AU - Hall, Duane D.
AU - Usachev, Yuriy M.
AU - McKnight, G. Stanley
AU - Hell, Johannes W
PY - 2007/11/28
Y1 - 2007/11/28
N2 - 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.
AB - 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.
KW - AKAP
KW - AMPA receptors
KW - Calcium
KW - PKA
KW - Synapse
UR - http://www.scopus.com/inward/record.url?scp=36549075142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36549075142&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601884
DO - 10.1038/sj.emboj.7601884
M3 - Article
C2 - 17972919
AN - SCOPUS:36549075142
VL - 26
SP - 4879
EP - 4890
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 23
ER -