Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2016 Oct 04;11340:11342-11347. doi: 10.1073/pnas.1604269113.
Show Gene links
Show Anatomy links
Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels.
Laursen WJ
,
Schneider ER
,
Merriman DK
,
Bagriantsev SN
,
Gracheva EO
.
???displayArticle.abstract???
The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 °C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by primary afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV1 orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV1 as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV1 orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV1, supporting functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV1-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV1 molecule, which can undergo profound tuning at the minimal cost of a single amino acid change.
Arrigoni,
Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.
2016, Pubmed
Arrigoni,
Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.
2016,
Pubmed
Bae,
Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin.
2016,
Pubmed
Bagriantsev,
Molecular mechanisms of temperature adaptation.
2015,
Pubmed
Bagriantsev,
Multiple modalities converge on a common gate to control K2P channel function.
2011,
Pubmed
Balayssac,
Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models.
2014,
Pubmed
Brauchi,
A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels.
2006,
Pubmed
Cao,
TRPV1 structures in distinct conformations reveal activation mechanisms.
2013,
Pubmed
Cao,
TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids.
2013,
Pubmed
Careau,
Stress-induced rise in body temperature is repeatable in free-ranging Eastern chipmunks (Tamias striatus).
2012,
Pubmed
Caterina,
Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
2000,
Pubmed
Caterina,
The capsaicin receptor: a heat-activated ion channel in the pain pathway.
1997,
Pubmed
,
Xenbase
Cavanaugh,
Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.
2011,
Pubmed
Cavanaugh,
Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons.
2011,
Pubmed
Chowdhury,
A molecular framework for temperature-dependent gating of ion channels.
2014,
Pubmed
Chuang,
Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
2001,
Pubmed
,
Xenbase
Clapham,
A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels.
2011,
Pubmed
Davis,
Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.
2000,
Pubmed
Feketa,
Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition.
2013,
Pubmed
Gao,
TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action.
2016,
Pubmed
Garami,
Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis.
2011,
Pubmed
Gracheva,
Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats.
2011,
Pubmed
Gracheva,
Evolutionary adaptation to thermosensation.
2015,
Pubmed
Grandl,
Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain.
2010,
Pubmed
Hanack,
GABA blocks pathological but not acute TRPV1 pain signals.
2015,
Pubmed
Hudson,
Metabolism, pulmocutaneous water loss and respiration of eight species of ground squirrels from different environments.
1973,
Pubmed
Jabba,
Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six.
2014,
Pubmed
Jara-Oseguera,
An external sodium ion binding site controls allosteric gating in TRPV1 channels.
2016,
Pubmed
Jordt,
Molecular basis for species-specific sensitivity to "hot" chili peppers.
2002,
Pubmed
Jordt,
Acid potentiation of the capsaicin receptor determined by a key extracellular site.
2000,
Pubmed
Julius,
TRP channels and pain.
2013,
Pubmed
Kobayashi,
Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors.
2005,
Pubmed
Lishko,
The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
2007,
Pubmed
Liu,
Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2.
2016,
Pubmed
Makhatadze,
Heat capacities of amino acids, peptides and proteins.
1998,
Pubmed
Mishra,
TRPV1-lineage neurons are required for thermal sensation.
2011,
Pubmed
Noël,
The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception.
2009,
Pubmed
Palkar,
The molecular and cellular basis of thermosensation in mammals.
2015,
Pubmed
Pang,
Selective keratinocyte stimulation is sufficient to evoke nociception in mice.
2015,
Pubmed
Paulsen,
Structure of the TRPA1 ion channel suggests regulatory mechanisms.
2015,
Pubmed
Pogorzala,
The cellular code for mammalian thermosensation.
2013,
Pubmed
Prescott,
A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.
2003,
Pubmed
,
Xenbase
Saito,
Evolution of Heat Sensors Drove Shifts in Thermosensation between Xenopus Species Adapted to Different Thermal Niches.
2016,
Pubmed
,
Xenbase
Schneider,
Temperature sensitivity of two-pore (K2P) potassium channels.
2014,
Pubmed
Tominaga,
The cloned capsaicin receptor integrates multiple pain-producing stimuli.
1998,
Pubmed
,
Xenbase
Yang,
Thermosensitive TRP channel pore turret is part of the temperature activation pathway.
2010,
Pubmed
Yao,
Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels.
2011,
Pubmed