IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23756-y.html
   My bibliography  Save this article

Allosteric modulation of ghrelin receptor signaling by lipids

Author

Listed:
  • Marjorie Damian

    (Université de Montpellier, ENSCM)

  • Maxime Louet

    (Université de Montpellier, ENSCM)

  • Antoniel Augusto Severo Gomes

    (Université de Montpellier, ENSCM
    Universidade Federal do Rio de Janeiro)

  • Céline M’Kadmi

    (Université de Montpellier, ENSCM)

  • Séverine Denoyelle

    (Université de Montpellier, ENSCM)

  • Sonia Cantel

    (Université de Montpellier, ENSCM)

  • Sophie Mary

    (Université de Montpellier, ENSCM)

  • Paulo M. Bisch

    (Universidade Federal do Rio de Janeiro)

  • Jean-Alain Fehrentz

    (Université de Montpellier, ENSCM)

  • Laurent J. Catoire

    (Université de Paris, Institut de Biologie Physico-Chimique (FRC 550))

  • Nicolas Floquet

    (Université de Montpellier, ENSCM)

  • Jean-Louis Banères

    (Université de Montpellier, ENSCM)

Abstract

The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects. We find that PIP2 shifts the conformational equilibrium of GHSR away from its inactive state, favoring basal and agonist-induced G protein activation. This occurs because of a preferential binding of PIP2 to specific intracellular sites in the receptor active state. Another lipid, GM3, also binds GHSR and favors G protein activation, but mostly in a ghrelin-dependent manner. Finally, we find that not only selective interactions but also the thickness of the bilayer reshapes the conformational repertoire of GHSR, with direct consequences on G protein selectivity. Taken together, this data illuminates the multifaceted role of the membrane components as allosteric modulators of how ghrelin signal could be propagated.

Suggested Citation

  • Marjorie Damian & Maxime Louet & Antoniel Augusto Severo Gomes & Céline M’Kadmi & Séverine Denoyelle & Sonia Cantel & Sophie Mary & Paulo M. Bisch & Jean-Alain Fehrentz & Laurent J. Catoire & Nicolas , 2021. "Allosteric modulation of ghrelin receptor signaling by lipids," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23756-y
    DOI: 10.1038/s41467-021-23756-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23756-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23756-y?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. Alexandre Pozza & François Giraud & Quentin Cece & Marina Casiraghi & Elodie Point & Marjorie Damian & Christel Le Bon & Karine Moncoq & Jean-Louis Banères & Ewen Lescop & Laurent J. Catoire, 2022. "Exploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Fabian Bumbak & James B. Bower & Skylar C. Zemmer & Asuka Inoue & Miquel Pons & Juan Carlos Paniagua & Fei Yan & James Ford & Hongwei Wu & Scott A. Robson & Ross A. D. Bathgate & Daniel J. Scott & Pau, 2023. "Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML314," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:12:y:2021:i:1:d:10.1038_s41467-021-23756-y. 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.