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 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.
Trifilieff
Pierre
P
CNRS, UMR 7102, Paris, France.
Lavaur
Jérémie
J
Pascoli
Vincent
V
Kappès
Vincent
V
Brami-Cherrier
Karen
K
Pagès
Christiane
C
Micheau
Jacques
J
Caboche
Jocelyne
J
Vanhoutte
Peter
P
D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly; D004705:Endocytosis / Q000187:drug effects*; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D050807:ets-Domain Protein Elk-1; D018698:Glutamic Acid; D019950:Mitogen-Activated Protein Kinase 1