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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Nature Portfolio
2017
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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) |
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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 |
work_keys_str_mv |
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_version_ |
1718394968960139264 |