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) |
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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 |
Keywords
- AKAP
- AMPA receptors
- Calcium
- PKA
- Synapse
ASJC Scopus subject areas
- Genetics
- Cell Biology