Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP
| Autor: | Robert F. Dallapiazza, Amy R Halt, Yuriy M. Usachev, Michael Weisenhaus, Yuan Lu, G. Stanley McKnight, Johannes W. Hell, Duane D. Hall, Margaret D. Allen |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Aging Time Factors Long-Term Potentiation A Kinase Anchor Proteins AMPA receptor Biology Hippocampal formation Hippocampus Article General Biochemistry Genetics and Molecular Biology Synapse Mice Postsynaptic potential Animals Homomeric Receptors AMPA Phosphorylation Long-term depression Molecular Biology General Immunology and Microbiology musculoskeletal neural and ocular physiology General Neuroscience Long-term potentiation Cyclic AMP-Dependent Protein Kinases Cell biology Mice Inbred C57BL nervous system Biochemistry Synapses Silent synapse Calcium |
| Zdroj: | The EMBO Journal. 26:4879-4890 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7601884 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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