Endocytosis controls glutamate-induced nuclear accumulation of ERK.

Pierre Trifilieff, Jérémie Lavaur, Vincent Pascoli, Vincent Kappès, Karen Brami-Cherrier, Christiane Pagès, Jacques Micheau, Jocelyne Caboche, Peter Vanhoutte
Molecular and Cellular Neuroscience. 2009-06-01; 41(3): 325-336
DOI: 10.1016/j.mcn.2009.04.006

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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.


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