State-dependent Ras signaling and AMPA receptor trafficking

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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DOI: 10.1101/gad.342205


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
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