IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v396y1998i6712d10.1038_25354.html
   My bibliography  Save this article

Heterodimerization is required for the formation of a functional GABAB receptor

Author

Listed:
  • Julia H. White

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Alan Wise

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Martin J. Main

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Andrew Green

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Neil J. Fraser

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Graham H. Disney

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Ashley A. Barnes

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Piers Emson

    (Babraham Institute)

  • Steven M. Foord

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

  • Fiona H. Marshall

    (Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre)

Abstract

GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its effects through ionotropic (GABAA/C) receptors to produce fast synaptic inhibition and metabotropic (GABAB) receptors to produce slow, prolonged inhibitory signals. The gene encoding a GABAB receptor (GABABR1) has been cloned1; however, when expressed in mammalian cells this receptor is retained as an immature glycoprotein on intracellular membranes2 and exhibits low affinity for agonists compared with the endogenous receptor on brain membranes. Here we report the cloning of a complementary DNA encoding a new subtype of the GABAB receptor (GABABR2), which we identified by mining expressed-sequence-tag databases. Yeast two-hybrid screening showed that this new GABABR2-receptor subtype forms heterodimers with GABABR1 through an interaction at their intracellular carboxy-terminal tails. Upon expression with GABABR2 in HEK293T cells, GABABR1 is terminally glycosylated and expressed at the cell surface. Co-expression of the two receptors produces a fully functional GABAB receptor at the cell surface; this receptor binds GABA with a high affinity equivalent to that of the endogenous brain receptor. These results indicate that, in vivo, functional brain GABAB receptors may be heterodimers composed of GABABR1 and GABABR2.

Suggested Citation

  • Julia H. White & Alan Wise & Martin J. Main & Andrew Green & Neil J. Fraser & Graham H. Disney & Ashley A. Barnes & Piers Emson & Steven M. Foord & Fiona H. Marshall, 1998. "Heterodimerization is required for the formation of a functional GABAB receptor," Nature, Nature, vol. 396(6712), pages 679-682, December.
  • Handle: RePEc:nat:nature:v:396:y:1998:i:6712:d:10.1038_25354
    DOI: 10.1038/25354
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/25354
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/25354?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Marie-Lise Jobin & Sana Siddig & Zsombor Koszegi & Yann Lanoiselée & Vladimir Khayenko & Titiwat Sungkaworn & Christian Werner & Kerstin Seier & Christin Misigaiski & Giovanna Mantovani & Markus Sauer, 2023. "Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. 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:nature:v:396:y:1998:i:6712:d:10.1038_25354. 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.