Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats

Yang-Yang Li; Qing-Yun Lv; Guan-Tao Zheng; Di Liu; Ji Ma; Gui-Mei He; Li-Biao Zhang; Shan Zheng; Hai-Peng Li; Yi-Hsuan Pan

doi:10.24272/j.issn.2095-8137.2021.209

Volume 43 Issue 1

Jan. 2022

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Article Navigation > Zoological Research > 2022 > 43(1): 52-63

Yang-Yang Li, Qing-Yun Lv, Guan-Tao Zheng, Di Liu, Ji Ma, Gui-Mei He, Li-Biao Zhang, Shan Zheng, Hai-Peng Li, Yi-Hsuan Pan. Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats. Zoological Research, 2022, 43(1): 52-63. doi: 10.24272/j.issn.2095-8137.2021.209

Citation:

Yang-Yang Li, Qing-Yun Lv, Guan-Tao Zheng, Di Liu, Ji Ma, Gui-Mei He, Li-Biao Zhang, Shan Zheng, Hai-Peng Li, Yi-Hsuan Pan. Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats. Zoological Research, 2022, 43(1): 52-63. doi: 10.24272/j.issn.2095-8137.2021.209

Citation:

Yang-Yang Li, Qing-Yun Lv, Guan-Tao Zheng, Di Liu, Ji Ma, Gui-Mei He, Li-Biao Zhang, Shan Zheng, Hai-Peng Li, Yi-Hsuan Pan. Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats. Zoological Research, 2022, 43(1): 52-63. doi: 10.24272/j.issn.2095-8137.2021.209

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Unexpected expression of heat-activated transient receptor potential (TRP) channels in winter torpid bats and cold-activated TRP channels in summer active bats

doi: 10.24272/j.issn.2095-8137.2021.209

Yang-Yang Li^{1, #},
Qing-Yun Lv^{1, #},
Guan-Tao Zheng¹,
Di Liu¹,
Ji Ma²,
Gui-Mei He³,
Li-Biao Zhang⁴,
Shan Zheng¹,
Hai-Peng Li^{5
,
,},
Yi-Hsuan Pan^{1
,
,}

1.
Key Laboratory of Brain Functional Genomics of Shanghai and Ministry of Education, School of Life Sciences, East China Normal University, Shanghai 200062, China
2.
School of Life Science, Department of Biomedical Science, East China Normal University, Shanghai 200062, China
3.
Institute of Eco-Chongming, School of Life Sciences, East China Normal University, Shanghai 200062, China
4.
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
5.
CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China

#Authors contributed equally to this work

Funds: This study was supported by the National Natural Science Foundation of China (31100273 to Y.H.P. and 91731304 to H.P.L.)

More Information

Corresponding author: E-mail: yihsuanp@gmail.com; lihaipeng@picb.ac.cn
Received Date: 2021-10-21
Accepted Date: 2021-11-17

Published Online: 2021-11-17

Publish Date: 2022-01-18

Abstract

Abstract

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.
- Hibernation,
- Bats,
- Brain,
- Thermo-TRPs

#Authors contributed equally to this work

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References(74)

References

[1]	Almeida MC, Hew-Butler T, Soriano RN, Rao S, Wang WY, Wang J, et al. 2012. Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. Journal of Neuroscience, 32(6): 2086−2099. doi: 10.1523/JNEUROSCI.5606-11.2012
[2]	Andrews MT. 2019. Molecular interactions underpinning the phenotype of hibernation in mammals. Journal of Experimental Biology, 222(2): jeb160606. doi: 10.1242/jeb.160606
[3]	Argyropoulos G, Harper ME. 2002. Invited review: uncoupling proteins and thermoregulation. Journal of Applied Physiology, 92(5): 2187−2198. doi: 10.1152/japplphysiol.00994.2001
[4]	Baez D, Raddatz N, Ferreira G, Gonzalez C, Latorre R. 2014. Gating of thermally activated channels. Current Topics in Membranes, 74: 51−87.
[5]	Barnes BM. 1989. Freeze avoidance in a mammal: body temperatures below 0 ^oC in an Arctic hibernator. Science, 244(4912): 1593−1595. doi: 10.1126/science.2740905
[6]	Bernal L, Sotelo-Hitschfeld P, König C, Sinica V, Wyatt A, Winter Z, et al. 2021. Odontoblast TRPC5 channels signal cold pain in teeth. Science Advances, 7(13): eabf5567. doi: 10.1126/sciadv.abf5567
[7]	Carey HV, Andrews MT, Martin SL. 2003. Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiological Reviews, 83(4): 1153−1181. doi: 10.1152/physrev.00008.2003
[8]	Carnesecchi J, Pinto PB, Lohmann I. 2018. Hox transcription factors: an overview of multi-step regulators of gene expression. International Journal of Developmental Biology, 62(11–12): 723–732.
[9]	Castillo K, Diaz-Franulic I, Canan J, Gonzalez-Nilo F, Latorre R. 2018. Thermally activated TRP channels: molecular sensors for temperature detection. Physical Biology, 15(2): 021001. doi: 10.1088/1478-3975/aa9a6f
[10]	Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. 1999. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature, 398(6726): 436−441. doi: 10.1038/18906
[11]	Cheshire Jr WP. 2016. Thermoregulatory disorders and illness related to heat and cold stress. Autonomic Neuroscience:Basic and Clinical, 196: 91−104. doi: 10.1016/j.autneu.2016.01.001
[12]	Dawe AR, Morrison PR. 1955. Characteristics of the hibernating heart. American Heart Journal, 49(3): 367−384. doi: 10.1016/0002-8703(55)90031-4
[13]	Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A. 2007. TRPM8 is required for cold sensation in mice. Neuron, 54(3): 371−378. doi: 10.1016/j.neuron.2007.02.024
[14]	Dhaka A, Viswanath V, Patapoutian A. 2006. Trp ion channels and temperature sensation. Annual Review of Neuroscience, 29: 135−161. doi: 10.1146/annurev.neuro.29.051605.112958
[15]	Diaz-Franulic I, Poblete H, Miño-Galaz G, González C, Latorre R. 2016. Allosterism and structure in thermally activated transient receptor potential channels. Annual Review of Biophysics, 45: 371−398. doi: 10.1146/annurev-biophys-062215-011034
[16]	Du GX, Tian YH, Yao ZH, Vu S, Zheng J, Chai LH, et al. 2020. A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds. Journal of Biological Chemistry, 295(28): 9641−9649. doi: 10.1074/jbc.RA120.013037
[17]	Ezquerra-Romano I, Ezquerra A. 2017. Highway to thermosensation: a traced review, from the proteins to the brain. Reviews in the Neurosciences, 28(1): 45−57. doi: 10.1515/revneuro-2016-0039
[18]	Feng Q. 2014. Temperature sensing by thermal TRP channels: thermodynamic basis and molecular insights. Current Topics in Membranes, 74: 19−50.
[19]	Fornes O, Castro-Mondragon JA, Khan A, van der Lee R, Zhang X, Richmond PA, et al. 2020. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Research, 48(D1): D87−D92.
[20]	French AR. 1985. Allometries of the durations of torpid and euthermic intervals during mammalian hibernation: a test of the theory of metabolic control of the timing of changes in body temperature. Journal of Comparative Physiology B, 156(1): 13−19. doi: 10.1007/BF00692921
[21]	Golozoubova V, Hohtola E, Matthias A, Jacobsson A, Cannon B, Nedergaard J. 2001. Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. The FASEB Journal, 15(11): 2048−2050. doi: 10.1096/fj.00-0536fje
[22]	Gracheva EO, Cordero-Morales JF, González-Carcacía JA, Ingolia NT, Manno C, Aranguren CI, et al. 2011. Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature, 476(7358): 88−91. doi: 10.1038/nature10245
[23]	Güler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M. 2002. Heat-evoked activation of the ion channel, TRPV4. Journal of Neuroscience, 22(15): 6408−6414. doi: 10.1523/JNEUROSCI.22-15-06408.2002
[24]	Han YJ, Zheng GT, Yang TX, Zhang SY, Dong D, Pan YH. 2015. Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in bats. BMC Evolutionary Biology, 15: 88. doi: 10.1186/s12862-015-0373-6
[25]	Hankenson FC, Marx JO, Gordon CJ, David JM. 2018. Effects of rodent thermoregulation on animal models in the research environment. Comparative Medicine, 68(6): 425−438. doi: 10.30802/AALAS-CM-18-000049
[26]	Himms-Hagen J. 1984. Nonshivering thermogenesis. Brain Research Bulletin, 12(2): 151−160. doi: 10.1016/0361-9230(84)90183-7
[27]	Hoffstaetter LJ, Bagriantsev SN, Gracheva EO. 2018. TRPs et al. : a molecular toolkit for thermosensory adaptations. Pflügers Archiv-European Journal of Physiology, 470(5): 745−759.
[28]	Huang JH, Zhang XM, McNaughton PA. 2006. Modulation of temperature-sensitive TRP channels. Seminars in Cell & Developmental Biology, 17(6): 638−645.
[29]	Huang WJ, Liao CC, Han YJ, Lv JY, Lei M, Li YY, et al. 2020. Co-activation of Akt, Nrf2, and NF-κB signals under UPR_ER in torpid Myotis ricketti bats for survival. Communications Biology, 3(1): 658. doi: 10.1038/s42003-020-01378-2
[30]	Jabba S, Goyal R, Sosa-Pagán JO, Moldenhauer H, Wu J, Kalmeta B, et al. 2014. Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six. Neuron, 82(5): 1017−1031. doi: 10.1016/j.neuron.2014.04.016
[31]	Jardín I, López JJ, Diez R, Sánchez-Collado J, Cantonero C, Albarrán L, et al. 2017. TRPs in pain sensation. Frontiers in Physiology, 8: 392. doi: 10.3389/fphys.2017.00392
[32]	Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, et al. 2009. TRPA1 acts as a cold sensor in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 106(4): 1273−1278. doi: 10.1073/pnas.0808487106
[33]	Kashio M. 2021. Thermosensation involving thermo-TRPs. Molecular and Cellular Endocrinology, 520: 111089. doi: 10.1016/j.mce.2020.111089
[34]	Klotz LO, Sánchez-Ramos C, Prieto-Arroyo I, Urbánek P, Steinbrenner H, Monsalve M. 2015. Redox regulation of FoxO transcription factors. Redox Biology, 6: 51−72. doi: 10.1016/j.redox.2015.06.019
[35]	Lambert SA, Jolma A, Campitelli LF, Das PK, Yin YM, Albu M, et al. 2018. The human transcription factors. Cell, 172(4): 650−665. doi: 10.1016/j.cell.2018.01.029
[36]	Laursen WJ, Mastrotto M, Pesta D, Funk OH, Goodman JB, Merriman DK, et al. 2015. Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation. Proceedings of the National Academy of Sciences of the United States of America, 112(5): 1607−1612. doi: 10.1073/pnas.1421419112
[37]	Laursen WJ, Schneider ER, Merriman DK, Bagriantsev SN, Gracheva EO. 2016. Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels. Proceedings of the National Academy of Sciences of the United States of America, 113(40): 11342−11347. doi: 10.1073/pnas.1604269113
[38]	Lazzeroni ME, Burbrink FT, Simmons NB. 2018. Hibernation in bats (Mammalia: Chiroptera) did not evolve through positive selection of leptin. Ecology and Evolution, 8(24): 12576−12596. doi: 10.1002/ece3.4674
[39]	Li YQ. 2010. Master stem cell transcription factors and signaling regulation. Cellular Reprogramming, 12(1): 3−13. doi: 10.1089/cell.2009.0033
[40]	Liu BY, Yao J, Zhu MX, Qin F. 2011. Hysteresis of gating underlines sensitization of TRPV3 channels. Journal of General Physiology, 138(5): 509−520. doi: 10.1085/jgp.201110689
[41]	Liu D, Zheng SH, Zheng GT, Lv QY, Shen B, Yuan XP, et al. 2018. Adaptation of the FK506 binding protein 1B to hibernation in bats. Cryobiology, 83: 1−8. doi: 10.1016/j.cryobiol.2018.07.004
[42]	Malik V, Zimmer D, Jauch R. 2018. Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming. Cellular and Molecular Life Sciences, 75(9): 1587−1612. doi: 10.1007/s00018-018-2748-5
[43]	Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2^{− ΔΔCT} method. Methods, 25(4): 402−408. doi: 10.1006/meth.2001.1262
[44]	Matos-Cruz V, Schneider ER, Mastrotto M, Merriman DK, Bagriantsev SN, Gracheva EO. 2017. Molecular prerequisites for diminished cold sensitivity in ground squirrels and hamsters. Cell Reports, 21(12): 3329−3337. doi: 10.1016/j.celrep.2017.11.083
[45]	Morin Jr P, Storey KB. 2009. Mammalian hibernation: differential gene expression and novel application of epigenetic controls. International Journal of Developmental Biology, 53(2–3): 433–442.
[46]	Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V, Kupko N, et al. 2021. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nature Structural & Molecular Biology, 28(7): 564−572.
[47]	Nelson CJ, Otis JP, Carey HV. 2009. A role for nuclear receptors in mammalian hibernation. The Journal of Physiology, 587(9): 1863−1870. doi: 10.1113/jphysiol.2008.167692
[48]	Nilius B, Owsianik G. 2011. The transient receptor potential family of ion channels. Genome Biology, 12(3): 218. doi: 10.1186/gb-2011-12-3-218
[49]	Palkar R, Lippoldt EK, McKemy DD. 2015. The molecular and cellular basis of thermosensation in mammals. Current Opinion in Neurobiology, 34: 14−19. doi: 10.1016/j.conb.2015.01.010
[50]	Pan YH, Zhang YJ, Cui J, Liu Y, McAllan BM, Liao CC, et al. 2013. Adaptation of phenylalanine and tyrosine catabolic pathway to hibernation in bats. PLoS One, 8(4): e62039. doi: 10.1371/journal.pone.0062039
[51]	Paricio-Montesinos R, Schwaller F, Udhayachandran A, Rau F, Walcher J, Evangelista R, et al. 2020. The sensory coding of warm perception. Neuron, 106(5): 830−841.e3. doi: 10.1016/j.neuron.2020.02.035
[52]	Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, et al. 2002. A heat-sensitive TRP channel expressed in keratinocytes. Science, 296(5575): 2046−2049. doi: 10.1126/science.1073140
[53]	Reeder DM, Frank CL, Turner GG, Meteyer CU, Kurta A, Britzke ER, et al. 2012. Frequent arousal from hibernation linked to severity of infection and mortality in bats with white-nose syndrome. PLoS One, 7(6): e38920. doi: 10.1371/journal.pone.0038920
[54]	Reményi A, Tomilin A, Schöler HR, Wilmanns M. 2002. Differential activity by DNA-induced quarternary structures of POU transcription factors. Biochemical Pharmacology, 64(5–6): 979–984.
[55]	Romero-Calvo I, Ocón B, Martínez-Moya P, Suárez MD, Zarzuelo A, Martínez-Augustin O, et al. 2010. Reversible Ponceau staining as a loading control alternative to actin in Western blots. Analytical Biochemistry, 401(2): 318−320. doi: 10.1016/j.ab.2010.02.036
[56]	Saito S, Tominaga M. 2015. Functional diversity and evolutionary dynamics of thermoTRP channels. Cell Calcium, 57(3): 214−221. doi: 10.1016/j.ceca.2014.12.001
[57]	Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, et al. 2002. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature, 418(6894): 186−190. doi: 10.1038/nature00894
[58]	Stones RC, Wiebers JE. 1965. A review of temperature regulation in bats (Chiroptera). The American Midland Naturalist, 74(1): 155−167. doi: 10.2307/2423129
[59]	Storey KB, Storey JM. 2010. Metabolic rate depression: the biochemistry of mammalian hibernation. Advances in Clinical Chemistry, 52: 78−108.
[60]	Talavera K, Startek JB, Alvarez-Collazo J, Boonen B, Alpizar YA, Sanchez A, et al. 2020. Mammalian transient receptor potential TRPA1 channels: from structure to disease. Physiological Reviews, 100(2): 725−803. doi: 10.1152/physrev.00005.2019
[61]	Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, et al. 2005. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature, 438(7070): 1022−1025. doi: 10.1038/nature04248
[62]	Tan CH, McNaughton PA. 2015. TRP channels in the sensation of heat. Madrid R and Bacigalupo J. In: Madrid R, Bacigalupo J. TRP Channels in Sensory Transduction. Cham: Springer, 165–183.
[63]	Teeling EC, Springer MS, Madsen O, Bates P, O'brien S J, Murphy WJ. 2005. A molecular phylogeny for bats illuminates biogeography and the fossil record. Science, 307(5709): 580−584. doi: 10.1126/science.1105113
[64]	Van Noort V, Snel B, Huynen MA. 2003. Predicting gene function by conserved co-expression. Trends in Genetics, 19(5): 238−242. doi: 10.1016/S0168-9525(03)00056-8
[65]	Vay L, Gu CJ, McNaughton PA. 2012. The thermo‐TRP ion channel family: properties and therapeutic implications. British Journal of Pharmacology, 165(4): 787−801. doi: 10.1111/j.1476-5381.2011.01601.x
[66]	Wang H, Siemens J. 2015. TRP ion channels in thermosensation, thermoregulation and metabolism. Temperature, 2(2): 178−187. doi: 10.1080/23328940.2015.1040604
[67]	Wang Y, Zhu TT, Ke SS, Fang N, Irwin DM, Lei M, et al. 2014. The great roundleaf bat (Hipposideros armiger) as a good model for cold-induced browning of intra-abdominal white adipose tissue. PLoS One, 9(11): e112495. doi: 10.1371/journal.pone.0112495
[68]	Webb PI, Speakman JR, Racey PA. 2011. How hot is a hibernaculum? A review of the temperatures at which bats hibernate. Canadian Journal of Zoology, 74(4): 761−765.
[69]	Xue HL, Wang Z, Hua YJ, Ke SS, Wang Y, Zhang JP, et al. 2018. Molecular signatures and functional analysis of beige adipocytes induced from in vivo intra-abdominal adipocytes. Science Advances, 4(7): eaar5319. doi: 10.1126/sciadv.aar5319
[70]	Yin QY, Ge HX, Liao CC, Liu D, Zhang SY, Pan YH. 2016. Antioxidant defenses in the brains of bats during hibernation. PLoS One, 11(3): e0152135. doi: 10.1371/journal.pone.0152135
[71]	Zhang Y, Morrone G, Zhang JX, Chen XA, Lu XL, Ma L, et al. 2003. CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein. EMBO Journal, 22(22): 6057−6067. doi: 10.1093/emboj/cdg577
[72]	Zholos AV. 2014. Trpc5. In: Nilius B, Flockerzi V. Mammalian Transient Receptor Potential (TRP) Cation Channels. Heidelberg: Springer.
[73]	Zhong J, Amina S, Liang MK, Akther S, Yuhi T, Nishimura T, et al. 2016. Cyclic ADP-Ribose and heat regulate oxytocin release via CD38 and TRPM2 in the hypothalamus during social or psychological stress in mice. Frontiers in Neuroscience, 10: 304.
[74]	Zimmermann K, Lennerz JK, Hein A, Link AS, Kaczmarek JS, Delling M, et al. 2011. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proceedings of the National Academy of Sciences of the United States of America, 108(44): 18114−18119. doi: 10.1073/pnas.1115387108