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Two single-point mutations in Ankyrin Repeat one drastically change the threshold temperature of TRPV1

Shogo Hori, Michihiro Tateyama, Tsuyoshi Shirai, Yoshihiro Kubo and Osamu Saitoh ()
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Shogo Hori: Nagahama Institute of Bio-Science and Technology
Michihiro Tateyama: Division of Biophysics and Neurobiology, National Institute for Physiological Sciences
Tsuyoshi Shirai: Nagahama Institute of Bio-Science and Technology
Yoshihiro Kubo: Division of Biophysics and Neurobiology, National Institute for Physiological Sciences
Osamu Saitoh: Nagahama Institute of Bio-Science and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract TRPV1 plays an important role in the thermosensory system; however, the mechanism controlling its heat activation property is not well understood. Here, we determine the heat activation properties of TRPV1 cloned from tailed amphibians, which prefer cooler environments, finding the threshold temperatures were approximately 10 °C lower compared with rat TRPV1 (rTRPV1). We find that two amino acid residues (Gln, Leu/Val) in the Ankyrin Repeat 1 (ANK1) region of the N-terminal domain are conserved among tailed amphibians and different from those (Arg, Lys) in rTRPV1. We observe the activation by heat in all urodelan TRPV1s is markedly elevated by substitution of these two amino acids. Conversely, reciprocal substitutions of rTRPV1 apparently lowers the high threshold temperature. Our studies demonstrate that tailed amphibians express TRPV1 with a reduced heat-activation threshold by substitution of two amino acid residues in the ANK1 region that likely contribute to cool-habitat selection.

Date: 2023
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DOI: 10.1038/s41467-023-38051-1

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