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Volume 14 Supplement 1

6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Receptor guanylyl cyclase-G is a novel thermosensor in Grueneberg ganglion neurons involved in coolness-induced ultrasonic distress calls in mice

BMC Pharmacology and Toxicology volume 14, Article number: P14 (2013) Cite this article

Background

In mammals, detection of ambient temperatures is mainly mediated by thermosensory neurons residing in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) [1–3]. Recently, neurons in the Grueneberg ganglion (GG) of the murine nasal vestibule have been found to be activated by cool temperatures [4, 5]. Unlike coolness-sensitive cells in the DRG and TG, neurons in the GG lack the TRPM8 channel [6] which is considered as a principal detector of cold [1–3]. Therefore, GG neurons are supposedly endowed with a so far unknown thermosensor. Interestingly, coolness-sensitive GG neurons express signaling elements associated with cyclic guanosine monophosphate (cGMP), including the cGMP-activated ion channel CNGA3 and receptor guanylyl cyclase-G (GC-G) [6–8]. Recent observations suggest that cGMP signaling is crucial for thermotransduction in the GG [8]. However, whether GC-G directly acts as a temperature sensor remains elusive.

Materials and methods

A combination of biochemical and molecular biology methods, Ca2+ imaging as well as behavioural studies comparing wild-type and GC-G-knockout mice was used to elucidate the molecular and biological function of GC-G in sensing cool temperatures.

Results

We show that GC-G is a thermosensory receptor that can be maximally stimulated by cool temperatures of about 15°C in both in vivo cellular cGMP accumulation assays and in vitro GC assays with a purified recombinant protein. Cells co-expressing GC-G and CNGA3 respond to cool temperatures via a rapid influx of calcium. Furthermore, we found a marked coolness-induced expression of the activity-dependent gene c-Fos in GG neurons of wild-type neonatal pups but not in GC-G-knockout conspecifics. Consistent with these findings, coolness-elicited ultrasonic vocalizations were significantly impaired in GC-G-knockout compared to wild-type pups.

Conclusion

Our data suggest that GC-G is a novel thermosensory protein and that GG activation via GC-G by coolness is critical for the generation of ultrasound calls by isolated pups to elicit maternal care.

References

  1. 1.

    Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D: The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007, 448: 204-208. 10.1038/nature05910.

  2. 2.

    Colburn RW, Lubin ML, Stone DJ, Wang Y, Lawrence D, D'Andrea MR, Brandt M, Liu Y, Flores CM, Qin N: Attenuated cold sensitivity in TRPM8 null mice. Neuron. 2007, 54: 379-386. 10.1016/j.neuron.2007.04.017.

  3. 3.

    Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A: TRPM8 is required for cold sensation in mice. Neuron. 2007, 54: 371-378. 10.1016/j.neuron.2007.02.024.

  4. 4.

    Mamasuew K, Breer H, Fleischer J: Grueneberg ganglion neurons respond to cool ambient temperatures. Eur J Neurosci. 2008, 28: 1775-1785. 10.1111/j.1460-9568.2008.06465.x.

  5. 5.

    Schmid A, Pyrski M, Biel M, Leinders-Zufal T, Zufall F: Grueneberg ganglion neurons are finely tuned cold sensors. J Neurosci. 2010, 30: 7563-7568. 10.1523/JNEUROSCI.0608-10.2010.

  6. 6.

    Fleischer J, Mamasuew K, Breer H: Expression of cGMP signaling elements in the Grueneberg ganglion. Histochem Cell Biol. 2009, 131: 75-88. 10.1007/s00418-008-0514-8.

  7. 7.

    Liu CY, Frase SE, Koos DS: Grueneberg ganglion olfactory subsystem employs a cGMP signaling pathway. J Comp Neurol. 2009, 516: 36-48. 10.1002/cne.22096.

  8. 8.

    Mamasuew K, Michalakis S, Breer H, Biel M, Fleischer J: The cyclic nucleotide-gated ion channel CNGA3 contributes to coolness-induced responses of Grueneberg ganglion neurons. Cell Mol Life Sci. 2010, 67: 1859-1869. 10.1007/s00018-010-0296-8.

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Author information

Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    • Ying-Chi Chao
    • , Yuh-Charn Lin
    • , Chih-Cheng Chen
    •  & Ruey-Bing Yang
  2. Institute of Physiology, University of Hohenheim, Stuttgart, Germany
    • Heinz Breer
    •  & Joerg Fleischer
  3. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
    • Ruey-Bing Yang
Authors
  1. Ying-Chi Chao
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  2. Heinz Breer
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  3. Yuh-Charn Lin
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  4. Chih-Cheng Chen
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  5. Joerg Fleischer
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  6. Ruey-Bing Yang
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Correspondence to Ruey-Bing Yang.

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Chao, Y., Breer, H., Lin, Y. et al. Receptor guanylyl cyclase-G is a novel thermosensor in Grueneberg ganglion neurons involved in coolness-induced ultrasonic distress calls in mice. BMC Pharmacol Toxicol 14, P14 (2013). https://doi.org/10.1186/2050-6511-14-S1-P14

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Keywords

  • Dorsal Root Ganglion
  • Cool Temperature
  • Trigeminal Ganglion
  • TRPM8 Channel
  • Ultrasonic Vocalization

BMC Pharmacology and Toxicology

ISSN: 2050-6511

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