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

Sci Rep. 2017 May 16;7(1):1944. doi: 10.1038/s41598-017-02021-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / blood
  • Adenylyl Cyclases / metabolism
  • Animals
  • Biomarkers
  • CREB-Binding Protein / metabolism
  • Cell Cycle Checkpoints
  • Cell Differentiation*
  • Cell Survival
  • Cells, Cultured
  • Corticotropin-Releasing Hormone / metabolism
  • Cyclic AMP / metabolism*
  • Humans
  • Mice
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / metabolism*
  • Receptors, Corticotropin-Releasing Hormone / metabolism*

Substances

  • Biomarkers
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Cyclic AMP
  • CREB-Binding Protein
  • Adenylyl Cyclases