Skip to main content
 

Orphan GPR110 targeted by N-docosahexaenoylethanolamine: an omega-3 fatty acid-dependent mechanism for brain development

Friday, September 18, 2015 — Poster Session V

2:00 p.m. – 3:30 p.m.
FAES Terrace
NIAAA
NEURO-55

Authors

  • JW Lee
  • G Kharebava
  • BX Huang
  • MA Rashid
  • S Patnaik
  • J Marugan
  • HY Kim

Abstract

Docosahexaenoic acid (DHA, 22:6n-3) is an omega-3 fatty acid essential for proper brain development and cognitive function. N-docosahexaenoylethanolamine (synaptamide), an endogenous metabolite of DHA, potently promotes neuritogenesis, synaptogensis and neurogenesis, however, the underlying molecular mechanism has not been determined. Here, we demonstrate that orphan G-protein coupled receptor 110 (GPR110) is the synaptamide receptor, mediating synaptamide-induced neurogenesis and neurite outgrowth in a cAMP-dependent manner. Mass spectrometry-based proteomic characterization and cellular fluorescence imaging probed by chemical analogues of synaptamide revealed specific binding of GPR110 to synaptamide. Disruption of this binding abolished but GPR110 overexpression enhanced synaptamide-induced bioactivity. GPR110 was highly expressed in fetal brains while their exposure to synaptamide significantly increased neurogenesis, indicating in vivo relevance of synaptamide/GPR110 signaling for neurodevelopment. GPR110 deorphanized as a functional synaptamide receptor provides a novel target for neurodevelopmental control and offers new insight into the mechanism by which omega-3 fatty acids promote brain development and function.

Category: Neuroscience