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

DEUSSING, JAN M.; ARMANDO, NATALIA G.; DOS SANTOS CLARO, PAULA A.; BONFIGLIO, JUAN JOSÉ; SILBERSTEIN, SUSANA; DEUSSING, JAN M.; SENIN, SERGIO A.; DOS SANTOS CLARO, PAULA A.; INDA, CAROLINA; SILBERSTEIN, SUSANA; SENIN, SERGIO A.; INDA, CAROLINA; ARMANDO, NATALIA G.; BONFIGLIO, JUAN JOSÉ

Scientific Reports

Nature Publishing Group

Lugar: Londres; Año: 2017 vol. 7 p. 1 - 17

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.