A single TRPV1 amino acid controls species sensitivity to capsaicin

Chu, Ying; Cohen, Bruce E.; Chuang, Huai-hu

doi:10.1038/s41598-020-64584-2

Title: A single TRPV1 amino acid controls species sensitivity to capsaicin

Journal Article · Fri May 15 00:00:00 EDT 2020 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-020-64584-2· OSTI ID:1631670

Chu, Ying ^[1]; Cohen, Bruce E. ^[2]; Chuang, Huai-hu ^[1]

Academia Sinica, Taipei (Taiwan). Institute of Molecular Biology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Chili peppers produce capsaicin (a vanilloid) that activates the transient receptor potential cation channel subfamily V member 1 (TRPV1) on sensory neurons to alter their membrane potential and induce pain. To identify residues responsible for differential TRPV1 capsaicin sensitivity among species, we used intracellular Ca²⁺ imaging to characterize chimeras composed of capsaicin-sensitive rat TRPV1 (rTRPV1) and capsaicin-insensitive chicken TRPV1 (cTRPV1) exposed to a series of capsaicinoids. We found that chimeras containing rat E570-V686 swapped into chicken receptors displayed capsaicin sensitivity, and that simply changing the alanine at position 578 in the S4-S5 helix of the chicken receptor to a glutamic acid was sufficient to endow it with capsaicin sensitivity in the micromolar range. Moreover, introduction of lysine, glutamine or proline at residue A578 also elicited capsaicin sensitivity in cTRPV1. Similarly, replacing corresponding rTRPV1 residue E570 with lysine or glutamine retained capsaicin sensitivity. The hydrophilic capsaicin analog Cap-EA activated a cTRPV1-A578E mutant, suggesting that A578 may participate in vanilloid binding. The hydrophilic vanilloid agonist zingerone did not activate any A578 mutants with capsaicin sensitivity, suggesting that the vanilloid group alone is not sufficient for receptor activation. Our study demonstrates that a subtle modification of TRPV1 in different species globally alters capsaicin responses.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); Ministry of Science and Technology

Grant/Contract Number:: AC02-05CH11231; NSC 102-2320-B-001-018-MY3

OSTI ID:: 1631670

Journal Information:: Scientific Reports, Vol. 10, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 19 works

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