Volume 14 Supplement 1

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

Open Access

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

  • Ying-Chi Chao1,
  • Heinz Breer2,
  • Yuh-Charn Lin1,
  • Chih-Cheng Chen1,
  • Joerg Fleischer2 and
  • Ruey-Bing Yang1, 3Email author
BMC Pharmacology and Toxicology201314(Suppl 1):P14

DOI: 10.1186/2050-6511-14-S1-P14

Published: 29 August 2013

Background

In mammals, detection of ambient temperatures is mainly mediated by thermosensory neurons residing in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) [13]. 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 [13]. 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) [68]. 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.

Authors’ Affiliations

(1)
Institute of Biomedical Sciences
(2)
Institute of Physiology, University of Hohenheim
(3)
Institute of Pharmacology, School of Medicine, National Yang-Ming University

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Copyright

© Chao et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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