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dc.contributor.author
Bonfiglio, Juan José
dc.contributor.author
Inda, Carolina
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Senin, Sergio Ariel
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Maccarrone, Giuseppina
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Refojo, Damian
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Giacomini, Damiana Paula
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Turck, Christoph W.
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Holsboer, Florian
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Arzt, Eduardo Simon
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Silberstein Cuña, Susana Iris
dc.date.available
2015-07-24T18:43:22Z
dc.date.issued
2013-03
dc.identifier.citation
Bonfiglio, Juan José; Inda, Carolina; Senin, Sergio Ariel; Maccarrone, Giuseppina; Refojo, Damian; et al.; B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells.; Endocrine Soc; Molecular Endocrinology; 27; 3-2013; 491-510
dc.identifier.issn
0888-8809
dc.identifier.issn
http://press.endocrine.org/doi/10.1210/me.2012-1359?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&
dc.identifier.uri
http://hdl.handle.net/11336/1488
dc.description.abstract
CRH is a key regulator of neuroendocrine, autonomic, and behavioral response to stress. CRH-stimulated CRH receptor 1 (CRHR1) activates ERK1/2 depending on intracellular context. In a previous work, we demonstrated that CRH activates ERK1/2 in limbic areas of the mouse brain (hippocampus and basolateral amygdala). ERK1/2 is an essential mediator of hippocampal physiological processes including emotional behavior, synaptic plasticity, learning, and memory. To elucidate the molecular mechanisms by which CRH activates ERK1/2 in hippocampal neurons, we used the mouse hippocampal cell line HT22. We document for the first time that ERK1/2 activation in response to CRH is biphasic, involving a first cAMP- and B-Raf-dependent early phase and a second phase that critically depends on CRHR1 internalization and ß-arrestin2. By means of mass-spectrometry-based screening, we identified B-Raf-associated proteins that coimmunoprecipitate with endogenous B-Raf after CRHR1 activation. Using molecular and pharmacological tools, the functional impact of selected B-Raf partners in CRH-dependent ERK1/2 activation was dissected. These results indicate that 14-3-3 proteins, protein kinase A, and Rap1, are essential for early CRH-induced ERK1/2 activation, whereas dynamin and vimentin are required for the CRHR1 internalization-dependent phase. Both phases of ERK1/2 activation depend on calcium influx and are affected by calcium/calmodulin-dependent protein kinase II inactivation. Thus, this report describes the dynamics and biphasic nature of ERK1/2 activation downstream neuronal CRHR1 and identifies several new critical components of the CRHR1 signaling machinery that selectively controls the early and late phases of ERK1/2 activation, thus providing new potential therapeutic targets for stress-related disorders.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Endocrine Soc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Crh Receptor 1
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Hippocampal
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Neurons
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Endocrinología y Metabolismo
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
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Otras Ciencias Médicas
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Otras Ciencias Médicas
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells.
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
27
dc.journal.pagination
491-510
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Bonfiglio, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Conicet -; Instituto P; Argentina;
dc.description.fil
Fil: Inda, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Conicet -; Instituto P; Argentina;
dc.description.fil
Fil: Senin, Sergio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Conicet -; Instituto P; Argentina;
dc.description.fil
Fil: Maccarrone, Giuseppina. Max-Planck-Institut Für Psychiatrie; Alemania;
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Fil: Refojo, Damian. Max-Planck-Institut Für Psychiatrie; Alemania;
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Fil: Giacomini, Damiana Paula. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Invest.bioquimicas de Bs.as(i); Argentina;
dc.description.fil
Fil: Turck, Christoph W.. Max-Planck-Institut Für Psychiatrie; Alemania;
dc.description.fil
Fil: Holsboer, Florian. Max-Planck-Institut Für Psychiatrie; Alemania;
dc.description.fil
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Conicet -; Instituto P; Argentina;
dc.description.fil
Fil: Silberstein, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Conicet -; Instituto P; Argentina;
dc.journal.title
Molecular Endocrinology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/?term=B-Raf+and+CRHR1+internalization+mediate+biphasic+ERK1%2F2+activation+by+CRH+in+hippocampal+HT22+cells
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