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Species differences and molecular determinant of TRPA1 cold sensitivity

Author

Listed:
  • Jun Chen

    (Neuroscience and Early Discovery)

  • Dawon Kang

    (The Chicago Medical School, Rosalind Franklin University of Medicine and Science
    Medical Research Centre for Neural Dysfunction, Institute of Health Sciences, Gyeongsang National University School of Medicine)

  • Jing Xu

    (Global Protein Science, Research and Development, AbbVie, Inc.)

  • Marc Lake

    (Global Protein Science, Research and Development, AbbVie, Inc.)

  • James O. Hogan

    (The Chicago Medical School, Rosalind Franklin University of Medicine and Science)

  • Chaohong Sun

    (Global Protein Science, Research and Development, AbbVie, Inc.)

  • Karl Walter

    (Global Protein Science, Research and Development, AbbVie, Inc.)

  • Betty Yao

    (Neuroscience and Early Discovery)

  • Donghee Kim

    (The Chicago Medical School, Rosalind Franklin University of Medicine and Science)

Abstract

TRPA1 is an ion channel and has been proposed as a thermosensor across species. In invertebrate and ancestral vertebrates such as fly, mosquito, frog, lizard and snakes, TRPA1 serves as a heat receptor, a sensory input utilized for heat avoidance or infrared detection. However, in mammals, whether TRPA1 is a receptor for noxious cold is highly controversial, as channel activation by cold was observed by some groups but disputed by others. Here we attribute the discrepancy to species differences. We show that cold activates rat and mouse TRPA1 but not human or rhesus monkey TRPA1. At the molecular level, a single residue within the S5 transmembrane domain (G878 in rodent but V875 in primate) accounts for the observed difference in cold sensitivity. This residue difference also underlies the species-specific effects of menthol. Together, our findings identify the species-specific cold activation of TRPA1 and reveal a molecular determinant of cold-sensitive gating.

Suggested Citation

  • Jun Chen & Dawon Kang & Jing Xu & Marc Lake & James O. Hogan & Chaohong Sun & Karl Walter & Betty Yao & Donghee Kim, 2013. "Species differences and molecular determinant of TRPA1 cold sensitivity," Nature Communications, Nature, vol. 4(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3501
    DOI: 10.1038/ncomms3501
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    Cited by:

    1. Lavanya Moparthi & Viktor Sinica & Vamsi K. Moparthi & Mohamed Kreir & Thibaut Vignane & Milos R. Filipovic & Viktorie Vlachova & Peter M. Zygmunt, 2022. "The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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