Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination
- Leipzig University, Germany
- University Hospital Würzburg, Germany
- University of Hamburg, Germany
- University of Würzburg, Germany
- University Hopsitals of Wuerzburg, Germany
Abstract
Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the Drosophila aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic in vivo experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased Cirl1 expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.
Data availability
The presented data are summarized in Tables 1-3.
Article and author information
Author details
Divya Sachidanandan
Funding
Deutsche Forschungsgemeinschaft (PA3241/2-1)
- Mareike Selcho
Deutsche Forschungsgemeinschaft (RI817/13-1)
- Heike L Rittner
Deutsche Forschungsgemeinschaft (FOR 2149/P03,TRR 166/B04,KI1460/4-1,KI1460/5-1)
- Robert J Kittel
Deutsche Forschungsgemeinschaft (SPP 1926/SO1337/2-2,SO1337/4-1)
- Peter Soba
Deutsche Forschungsgemeinschaft (FOR 2149/P01 and P03)
- Tobias Langenhan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Ethics
Animal experimentation: Animal care and protocols were performed in accordance with international guidelines for the care and use of laboratory animals (EU Directive 2010/63/EU for animal experiments) and were approved by the Government of Unterfranken (protocol numbers 2-733 and 2-264).
Version history
- Received: March 13, 2020
- Accepted: September 17, 2020
- Accepted Manuscript published: September 30, 2020 (version 1)
- Version of Record published: October 9, 2020 (version 2)
Copyright
© 2020, Dannhäuser et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination
eLife 9:e56738.
https://doi.org/10.7554/eLife.56738
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