Endocytosis controls glutamate-induced nuclear accumulation of ERK

Nuclear translocation of activated extracellular signal-regulated kinases (ERK) in neurons is critical for gene regulations underlying long-term neuronal adaptation and memory formation. However, it is unknown how activated ERK travel from the post-synaptic elements where their activation occurs, to...

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Published in:Molecular and cellular neuroscience 2009-06, Vol.41 (3), p.325-336
Main Authors: Trifilieff, Pierre, Lavaur, Jérémie, Pascoli, Vincent, Kappès, Vincent, Brami-Cherrier, Karen, Pagès, Christiane, Micheau, Jacques, Caboche, Jocelyne, Vanhoutte, Peter
Format: Article
Language:English
Subjects:
AMPA receptors
Animals
Cell Culture Techniques
Cell Line
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cercopithecus aethiops
Chromatin Assembly and Disassembly
Elk-1
Endocytosis - drug effects
Enzyme Activation
ets-Domain Protein Elk-1 - metabolism
Glutamic Acid - pharmacology
Histone
Immediate early genes
Life Sciences
MAP kinase signaling
Mitogen-Activated Protein Kinase 1 - metabolism
MSK-1
Neurons - drug effects
Neurons - metabolism
Neurons and Cognition
Protein Transport - drug effects
Rats
Receptors, AMPA - metabolism
Receptors, Glutamate - metabolism
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Summary:Nuclear translocation of activated extracellular signal-regulated kinases (ERK) in neurons is critical for gene regulations underlying long-term neuronal adaptation and memory formation. However, it is unknown how activated ERK travel from the post-synaptic elements where their activation occurs, to the nucleus where they translocate to exert their transcriptional roles. In cultured neurons, we identified endocytosis as a prime event in glutamate-induced nuclear trafficking of ERK2. We show that glutamate triggers a rapid recruitment of ERK2 to a protein complex comprising markers of the clathrin-dependent endocytotic and AMPA/glutamate receptor subtype. Inhibition of endocytosis results in a neuritic withholding of activated ERK2 without modification of ERK2 activity. As a consequence, endocytosis blockade alters ERK-dependent nuclear events, such as mitogen and stressed-activated kinase-1 (MSK-1) activation, histone H3 phosphorylation and gene regulations. Our data provide the first evidence that the endocytic pathway controls ERK nuclear translocation and ERK-dependent gene regulations induced by glutamate.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2009.04.006