Article abstract
Nature Chemical Biology 5, 183 - 190 (2009)
Published online: 8 February 2009 | doi:10.1038/nchembio.146
Zinc activates damage-sensing TRPA1 ion channels
Hongzhen Hu1,4, Michael Bandell1,4, Matt J Petrus1, Michael X Zhu2 & Ardem Patapoutian1,3
Abstract
Zinc is an essential biological trace element. It is required for the structure or function of over 300 proteins, and it is increasingly recognized for its role in cell signaling. However, high concentrations of zinc have cytotoxic effects, and overexposure to zinc can cause pain and inflammation through unknown mechanisms. Here we show that zinc excites nociceptive somatosensory neurons and causes nociception in mice through TRPA1, a cation channel previously shown to mediate the pungency of wasabi and cinnamon through cysteine modification. Zinc activates TRPA1 through a unique mechanism that requires zinc influx through TRPA1 channels and subsequent activation via specific intracellular cysteine and histidine residues. TRPA1 is highly sensitive to intracellular zinc, as low nanomolar concentrations activate TRPA1 and modulate its sensitivity. These findings identify TRPA1 as an important target for the sensory effects of zinc and support an emerging role for zinc as a signaling molecule that can modulate sensory transmission.
- Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
- Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, Columbus, Ohio 43210, USA.
- Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
- These authors contributed equally to this work.
Correspondence to: Ardem Patapoutian1,3 e-mail: apatapou@gnf.org
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Intracellular zinc irritates TRPA1Nature Chemical Biology News and Views (01 Mar 2009)
Channeling painNature Medicine News and Views (01 May 2006)
RESEARCH
Lymphotoxin pathway directs thymic Aire expressionNature Immunology Article (01 Nov 2003)
A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlicNature Neuroscience Article (01 Mar 2008)
See all 37 matches for Research
