IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13123.html
   My bibliography  Save this article

Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function

Author

Listed:
  • Ji-Won Lee

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • Bill X. Huang

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • HeungSun Kwon

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • Md Abdur Rashid

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • Giorgi Kharebava

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • Abhishek Desai

    (Laboratory of Molecular Signaling, NIAAA, NIH)

  • Samarjit Patnaik

    (National Center for Advancement of Translational Sciences (NCATS), NIH)

  • Juan Marugan

    (National Center for Advancement of Translational Sciences (NCATS), NIH)

  • Hee-Yong Kim

    (Laboratory of Molecular Signaling, NIAAA, NIH)

Abstract

Docosahexaenoic acid (DHA, 22:6n-3) is an omega-3 fatty acid essential for proper brain development. N-docosahexaenoylethanolamine (synaptamide), an endogenous metabolite of DHA, potently promotes neurogenesis, neuritogenesis and synaptogenesis; however, the underlying molecular mechanism is not known. Here, we demonstrate orphan G-protein coupled receptor 110 (GPR110, ADGRF1) as the synaptamide receptor, mediating synaptamide-induced bioactivity in a cAMP-dependent manner. Mass spectrometry-based proteomic characterization and cellular fluorescence tracing with chemical analogues of synaptamide reveal specific binding of GPR110 to synaptamide, which triggers cAMP production with low nM potency. Disruption of this binding or GPR110 gene knockout abolishes while GPR110 overexpression enhances synaptamide-induced bioactivity. GPR110 is highly expressed in fetal brains but rapidly decreases after birth. GPR110 knockout mice show significant deficits in object recognition and spatial memory. GPR110 deorphanized as a functional synaptamide receptor provides a novel target for neurodevelopmental control and new insight into mechanisms by which DHA promotes brain development and function.

Suggested Citation

  • Ji-Won Lee & Bill X. Huang & HeungSun Kwon & Md Abdur Rashid & Giorgi Kharebava & Abhishek Desai & Samarjit Patnaik & Juan Marugan & Hee-Yong Kim, 2016. "Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function," Nature Communications, Nature, vol. 7(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13123
    DOI: 10.1038/ncomms13123
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13123
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13123?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xinyan Zhu & Yu Qian & Xiaowan Li & Zhenmei Xu & Ruixue Xia & Na Wang & Jiale Liang & Han Yin & Anqi Zhang & Changyou Guo & Guangfu Wang & Yuanzheng He, 2022. "Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Daniel T. D. Jones & Andrew N. Dates & Shaun D. Rawson & Maggie M. Burruss & Colin H. Lipper & Stephen C. Blacklow, 2023. "Tethered agonist activated ADGRF1 structure and signalling analysis reveal basis for G protein coupling," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13123. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.