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Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines

Author

Listed:
  • Lindsey J. Macpherson

    (The Scripps Research Institute)

  • Adrienne E. Dubin

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Michael J. Evans

    (The Scripps Research Institute)

  • Felix Marr

    (The Scripps Research Institute
    Westfälische Wilhelms-Universität Münster)

  • Peter G. Schultz

    (The Scripps Research Institute
    Genomics Institute of the Novartis Research Foundation)

  • Benjamin F. Cravatt

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Ardem Patapoutian

    (The Scripps Research Institute
    Genomics Institute of the Novartis Research Foundation)

Abstract

Sensing danger The TRPA1 ion channel, found in neurons associated with sensing pain, responds to noxious and pungent compounds and also to cold. Gene knockout experiments in mice confirm that TRPA1 is a physiologicallyrequired pain sensor. How such diverse stimuli activate TRPA1 was not known but Macpherson et al. show that that TRPA1 is activated by covalent modification of its cysteine residues. It is not unusual for proteins to be modified by cysteine reactive agents, but this is the first ion channel known to be activated by this method. The role of TRPA1 activation in response to electrophile toxicity and oxidative stress may be to warn the organism of potential tissue damage.

Suggested Citation

  • Lindsey J. Macpherson & Adrienne E. Dubin & Michael J. Evans & Felix Marr & Peter G. Schultz & Benjamin F. Cravatt & Ardem Patapoutian, 2007. "Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines," Nature, Nature, vol. 445(7127), pages 541-545, February.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7127:d:10.1038_nature05544
    DOI: 10.1038/nature05544
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    Cited by:

    1. Xiaoning Wang & Yangyang Sun & Qian Wang & Fengying Liu & Weijie Yang & Xin Sui & Jun Yang & Minmin Zhang & Shuai Wang & Zhenyu Xiao & Yuan Luo & Yongan Wang & Tong Zhu, 2022. "Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation," IJERPH, MDPI, vol. 19(13), pages 1-18, June.
    2. A. Catalina Vélez-Ortega & Ruben Stepanyan & Stephanie E. Edelmann & Sara Torres-Gallego & Channy Park & Desislava A. Marinkova & Joshua S. Nowacki & Ghanshyam P. Sinha & Gregory I. Frolenkov, 2023. "TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Avnika Bali & Samantha P. Schaefer & Isabelle Trier & Alice L. Zhang & Lilian Kabeche & Candice E. Paulsen, 2023. "Molecular mechanism of hyperactivation conferred by a truncation of TRPA1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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