IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v440y2006i7088d10.1038_nature04700.html
   My bibliography  Save this article

A voltage-gated proton-selective channel lacking the pore domain

Author

Listed:
  • I. Scott Ramsey

    (Harvard Medical School)

  • Magdalene M. Moran

    (Harvard Medical School
    Hydra Biosciences)

  • Jayhong A. Chong

    (Harvard Medical School
    Hydra Biosciences)

  • David E. Clapham

    (Harvard Medical School)

Abstract

Voltage changes across the cell membrane control the gating of many cation-selective ion channels. Conserved from bacteria to humans1, the voltage-gated-ligand superfamily of ion channels are encoded as polypeptide chains of six transmembrane-spanning segments (S1–S6). S1–S4 functions as a self-contained voltage-sensing domain (VSD), in essence a positively charged lever that moves in response to voltage changes. The VSD ‘ligand’ transmits force via a linker to the S5–S6 pore domain ‘receptor’2, thereby opening or closing the channel. The ascidian VSD protein Ci-VSP gates a phosphatase activity rather than a channel pore, indicating that VSDs function independently of ion channels3. Here we describe a mammalian VSD protein (HV1) that lacks a discernible pore domain but is sufficient for expression of a voltage-sensitive proton-selective ion channel activity. Hv1 currents are activated at depolarizing voltages, sensitive to the transmembrane pH gradient, H+-selective, and Zn2+-sensitive. Mutagenesis of Hv1 identified three arginine residues in S4 that regulate channel gating and two histidine residues that are required for extracellular inhibition of Hv1 by Zn2+. Hv1 is expressed in immune tissues and manifests the characteristic properties of native proton conductances ( G vH + ). In phagocytic leukocytes4, G vH + are required to support the oxidative burst that underlies microbial killing by the innate immune system4,5. The data presented here identify Hv1 as a long-sought voltage-gated H+ channel and establish Hv1 as the founding member of a family of mammalian VSD proteins.

Suggested Citation

  • I. Scott Ramsey & Magdalene M. Moran & Jayhong A. Chong & David E. Clapham, 2006. "A voltage-gated proton-selective channel lacking the pore domain," Nature, Nature, vol. 440(7088), pages 1213-1216, April.
  • Handle: RePEc:nat:nature:v:440:y:2006:i:7088:d:10.1038_nature04700
    DOI: 10.1038/nature04700
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature04700
    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/nature04700?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. Chang Zhao & Parker D. Webster & Alexis Angeli & Francesco Tombola, 2023. "Mechanically-primed voltage-gated proton channels from angiosperm plants," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Lifeng Tian & Hao Zhang & Shilong Yang & Anna Luo & Peter Muiruri Kamau & Jingmei Hu & Lei Luo & Ren Lai, 2023. "Vertebrate OTOP1 is also an alkali-activated channel," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Elena Grahn & Svenja V. Kaufmann & Malika Askarova & Momchil Ninov & Luisa M. Welp & Thomas K. Berger & Henning Urlaub & U.Benjamin Kaupp, 2023. "Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:440:y:2006:i:7088:d:10.1038_nature04700. 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.