Molecular Prerequisites for Diminished Cold Sensitivity in Ground Squirrels and Hamsters

Vanessa Matos-Cruz, Eve R. Schneider, Marco Mastrotto, Dana K. Merriman, Sviatoslav N. Bagriantsev, Elena O. Gracheva

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Thirteen-lined ground squirrels and Syrian hamsters are known for their ability to withstand cold during hibernation. We found that hibernators exhibit cold tolerance even in the active state. Imaging and electrophysiology of squirrel somatosensory neurons reveal a decrease in cold sensitivity of TRPM8-expressing cells. Characterization of squirrel and hamster TRPM8 showed that the channels are chemically activated but exhibit poor activation by cold. Cold sensitivity can be re-introduced into squirrel and hamster TRPM8 by transferring the transmembrane domain from the cold sensitive rat ortholog. The same can be achieved in squirrel TRPM8 by mutating only six amino acids. Reciprocal mutations suppress cold sensitivity of the rat ortholog, supporting functional significance of these residues. Our results suggest that ground squirrels and hamsters exhibit reduced cold sensitivity, partially due to modifications in the transmembrane domain of TRPM8. Our study reveals molecular adaptations that accompany cold tolerance in two species of mammalian hibernators. Matos-Cruz et al. show that ground squirrels and hamsters exhibit cold tolerance even in the active non-hibernating state, partially due to independent modifications in the core transmembrane domain of the cold-sensing channel, TRPM8. The study reveals molecular adaptations that accompany cold tolerance in two species of active mammalian hibernators.

Original languageEnglish
Pages (from-to)3329-3337
Number of pages9
JournalCell Reports
Volume21
Issue number12
DOIs
StatePublished - Dec 19 2017

Bibliographical note

Funding Information:
We thank members of the Gracheva and Bagriantsev laboratories for their contributions throughout the project. This study was partly funded by fellowships from the Beckman Foundation and the Rita Allen Foundation and NIH grants 1R01NS091300-01A1 and 3R01NS091300-02S1 to E.O.G; by American Heart Association grant 14SDG17880015 and NSF grant 1453167 to S.N.B.; and by the Axle Tech International Endowed Professorship to D.K.M. V.M.-C. was partially supported by an NSF Postdoctoral Fellowship ( 1306144 ). E.R.S. was supported by a postdoctoral fellowship from the Arnold and Mabel Beckman Foundation .

Publisher Copyright:
© 2017 The Author(s)

Keywords

  • Syrian hamster
  • TRPM8
  • cold sensitivity
  • ground squirrel
  • sensory adaptation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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