Qin, Y., Zhu, Y. H., Baumgart, J. P., Stornetta, R. L., Seidenman, K., Mack, V., van Aelst, L., Zhu, J. J. (September 2005) State-dependent Ras signaling and AMPA receptor trafficking. Genes & Development, 19 (17). pp. 2000-2015. ISSN 0890-9369
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Abstract
Synaptic trafficking of AMPA-Rs, controlled by small GTPase Ras signaling, plays a key role in synaptic plasticity. However, how Ras signals synaptic AMPA-R trafficking is unknown. Here we show that low levels of Ras activity stimulate extracellular.signal-regulated kinase kinase (MEK)-p42/44 MAPK (extracellular signal-regulated kinase [ERK]) signaling, whereas high levels of Ras activity stimulate additional Pi3 kinase (Pi3K)-protein kinase B (PKB) signaling, each accounting for similar to 50% of the potentiation during long-term potentiation (LTP). Spontaneous neural activity stimulates the Ras-MEK-ERK pathway that drives GluR2L into synapses. In the presence of neuromodulator agonists, neural activity also stimulates the Ras-Pi3K-PKB pathway that drives GluR1 into synapses. Neuromodulator release increases with increases of vigilance. Correspondingly, Ras-MEK-ERK activity in sleeping animals is sufficient to deliver GluR2L into synapses, while additional increased Ras-Pi3K-PKB activity in awake animals delivers GluR1 into synapses. Thus, state-dependent Ras signaling, which specifies downstream MEK-ERK and Pi3K-PKB pathways, differentially control GluR2L- and GluR1-dependent synaptic plasticity.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Ras Erk Pi3 kinase Src synaptic plasticity neuromodulators behavioral states Activated Protein Kinase Long Term potentiation long-term potentiation HIPPOCAMPAL SYNAPTIC PLASTICITY NR2B-CONTAINING NMDA RECEPTORS EPIDERMAL-GROWTH-FACTOR BETA-GAMMA-SUBUNITS GLUTAMATE RECEPTORS B-RAF MUSCARINIC RECEPTORS COUPLED RECEPTORS |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor bioinformatics > genomics and proteomics > genetics & nucleic acid processing > Long term potentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity |
| CSHL Authors: | |
| Communities: | CSHL labs > Van Aelst lab |
| Depositing User: | CSHL Librarian |
| Date: | September 2005 |
| Date Deposited: | 06 Jan 2012 15:15 |
| Last Modified: | 22 Feb 2017 20:04 |
| PMCID: | PMC1199571 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22683 |
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