Exchange protein directly activated by cAMP 2 is required for corticotropin-releasing hormone-mediated spine loss

Zhong Xie, Peter Penzes*, Deepak P. Srivastava

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Corticotropin-releasing hormone is produced in response to acute and chronic stress. Previous studies have shown that activation of the corticotropin-releasing hormone receptor 1 (CRHR1) by corticotropin-releasing hormone results in the rapid loss of dendritic spines which correlates with cognitive dysfunction associated with stress. Exchange protein directly activated by cAMP (EPAC2), a guanine nucleotide exchange factor for the small GTPase Rap, plays a critical role in regulating dendritic spine morphology and has been linked with CRHR1 signalling. In this study, we have tested whether EPAC2 links corticotropin-releasing hormone with dendritic spine remodelling. In primary rat cortical neurons, we show that CRHR1 is highly enriched in the dendritic spines. Furthermore, we find that EPAC2 and CRHR1 co-localize in cortical neurons and that acute exposure to corticotropin-releasing hormone induces spine loss. To establish whether EPAC2 was required for corticotropin-releasing hormone–mediated spine loss, we knocked-down EPAC2 in cortical neurons using a short hairpin RNA-mediated approach. In the presence of Epac2 knocked-down, corticotropin-releasing hormone was no longer able to induce spine loss. Taken together, our data indicate that EPAC2 is required for the rapid loss of dendritic spines induced by corticotropin-releasing hormone and may ultimately contribute to responses to acute stress.

Original languageEnglish (US)
Pages (from-to)3108-3114
Number of pages7
JournalEuropean Journal of Neuroscience
Volume50
Issue number7
DOIs
StatePublished - Oct 1 2019

Keywords

  • cortical neurons
  • dendritic spine
  • excitatory synapse
  • rap
  • small GTPase
  • stress

ASJC Scopus subject areas

  • Neuroscience(all)

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