Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 72
Glutamate-induced synapse-to-nucleus shuttling of ERK and the transcription factor
Elk-1 in striatal neurons requires vesicular transport.
Trifilieff P1,2; Lavaur J1 ; Brami-Cherrier K1 ; Pagès C1; Micheau J2 ; Caboche J1
and Vanhoutte P1
1Lab. Signalisation Neuronale et Régulations Géniques-Univ. Pierre et Marie Curie
Paris 6-CNRS-UMR7102.
2 Lab. Neurosciences Cognitives-Univ. Bordeaux I-CNRS-UMR5106.
MAP kinases of the ERK subtype (Extracellular signal-Regulated Kinase) play a critical role
in long term neuronal adaptations, learning and memory. These long term events require gene
regulations that depend on the presence of activated ERKs in the nucleus. ERKs are expressed
and activated in neurites, at considerable distance from the nucleus, and shuttle towards the
nucleus upon activation by a mechanism that is not clearly defined yet. Furthermore, we have
previously shown that one characteristic of neuronal cells is that the transcription factor Elk-1,
one of the major ERKs’ target, has the same expression pattern as ERK and is expressed in
both cytoplasmic and nuclear compartments.
In the present study, we analysed the sub-cellular fate of ERK and Elk-1 in a model of ERKdependent
Immediate Early Gene (IEG) induction on striatal neurons. We show that ERK and
Elk-1 rapidly translocate to the nucleus upon stimulation with the same kinetics. Confocal
analysis of ERK and Elk-1 staining reveal a “clustered” pattern with a high degree of colocalization
with clathrin-coated vesicle (CCV) markers. Co-immunoprecipitation assays
show an interaction of ERK and Elk-1 with markers of CCV, which is transiently increased
upon stimulation. Despite the fact that glutamate stimulates endocytosis of both ionotropic
and metabotropic glutamate receptors, we establish that ERK interact specifically with
AMPA-containing vesicles. Interestingly, blockade of endocytosis inhibits glutamatedependent
ERK and Elk-1 nuclear translocation without alteration of neither ERK activation
nor activation of other MAP kinases. In our model, where inhibition of vesicular transport
restricts ERK activation to the cytoplasm, we measured the consequences of the absence of
nuclear translocation of activated ERKs. We underline the multiple roles of ERKs in this
compartment and show their functions as key regulators of IEG expression as well as
modulators of chromatin structure via the control of histone phosphorylation. This study
underlies the key role of the vesicular transport in the synase-to-nucleus shuttling of ERK. We
are currently analyzing the functional relevance of the vesicular transport-mediated ERK
nuclear translocation in the establishment of plasticity in the striatum in vivo.
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