Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines

Lindsey J. Macpherson, Adrienne E. Dubin, Michael J. Evans, Felix Marr, Peter G. Schultz, Benjamin F. Cravatt and Ardem Patapoutian ()
Additional contact information
Lindsey J. Macpherson: The Scripps Research Institute
Adrienne E. Dubin: The Scripps Research Institute
Michael J. Evans: The Scripps Research Institute
Felix Marr: The Scripps Research Institute
Peter G. Schultz: The Scripps Research Institute
Benjamin F. Cravatt: The Scripps Research Institute
Ardem Patapoutian: The Scripps Research Institute

Nature, 2007, vol. 445, issue 7127, 541-545

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.

Date: 2007
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DOI: 10.1038/nature05544

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