cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells

Abstract Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (G...

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Autores principales: Carolina Inda, Juan José Bonfiglio, Paula A. dos Santos Claro, Sergio A. Senin, Natalia G. Armando, Jan M. Deussing, Susana Silberstein
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/18a1ff3e3a154fb0897d2fe370ba4859
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spelling oai:doaj.org-article:18a1ff3e3a154fb0897d2fe370ba48592021-12-02T11:52:35ZcAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells10.1038/s41598-017-02021-72045-2322https://doaj.org/article/18a1ff3e3a154fb0897d2fe370ba48592017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02021-7https://doaj.org/toc/2045-2322Abstract Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation and c-fos induction, but only sAC-generated cAMP pools are critical for the neuritogenic effect of CRH, further highlighting the engagement of two sources of cAMP downstream of the activation of a GPCR, and reinforcing the notion that restricted cAMP microdomains may regulate independent cellular processes.Carolina IndaJuan José BonfiglioPaula A. dos Santos ClaroSergio A. SeninNatalia G. ArmandoJan M. DeussingSusana SilbersteinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Carolina Inda
Juan José Bonfiglio
Paula A. dos Santos Claro
Sergio A. Senin
Natalia G. Armando
Jan M. Deussing
Susana Silberstein
cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
description Abstract Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade. Both tmACs and sAC are involved in corticotropin-releasing hormone (CRH)-mediated CREB phosphorylation and c-fos induction, but only sAC-generated cAMP pools are critical for the neuritogenic effect of CRH, further highlighting the engagement of two sources of cAMP downstream of the activation of a GPCR, and reinforcing the notion that restricted cAMP microdomains may regulate independent cellular processes.
format article
author Carolina Inda
Juan José Bonfiglio
Paula A. dos Santos Claro
Sergio A. Senin
Natalia G. Armando
Jan M. Deussing
Susana Silberstein
author_facet Carolina Inda
Juan José Bonfiglio
Paula A. dos Santos Claro
Sergio A. Senin
Natalia G. Armando
Jan M. Deussing
Susana Silberstein
author_sort Carolina Inda
title cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
title_short cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
title_full cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
title_fullStr cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
title_full_unstemmed cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells
title_sort camp-dependent cell differentiation triggered by activated crhr1 in hippocampal neuronal cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/18a1ff3e3a154fb0897d2fe370ba4859
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AT juanjosebonfiglio campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
AT paulaadossantosclaro campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
AT sergioasenin campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
AT nataliagarmando campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
AT janmdeussing campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
AT susanasilberstein campdependentcelldifferentiationtriggeredbyactivatedcrhr1inhippocampalneuronalcells
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