A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli
Abstract Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatiotemporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-09-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202110514 |
| _version_ | 1826990454864871424 |
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| author | Rotem Ruach Shai Yellinek Eyal Itskovits Noa Deshe Yifat Eliezer Eduard Bokman Alon Zaslaver |
| author_facet | Rotem Ruach Shai Yellinek Eyal Itskovits Noa Deshe Yifat Eliezer Eduard Bokman Alon Zaslaver |
| author_sort | Rotem Ruach |
| collection | DOAJ |
| description | Abstract Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatiotemporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in Caenorhabditis elegans animals can cell‐autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly changing continuous gradients. This encoding relies on a simple negative feedback in the G‐protein‐coupled receptor (GPCR) signaling pathway in which TAX‐6/Calcineurin plays a key role in mediating the feedback inhibition. This negative feedback supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient's first derivative. A simple mathematical model explains the fine neural dynamics of both wild‐type and tax‐6 mutant animals, further highlighting how the calcium‐dependent activity of TAX‐6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a general solution for efficient cell‐autonomous coding of external stimuli. |
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| format | Article |
| id | doaj.art-9d836596b3904b0d9ef88f5d2de92434 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2025-02-18T08:20:49Z |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-9d836596b3904b0d9ef88f5d2de924342024-11-03T12:55:04ZengSpringer NatureMolecular Systems Biology1744-42922022-09-0118911610.15252/msb.202110514A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuliRotem Ruach0Shai Yellinek1Eyal Itskovits2Noa Deshe3Yifat Eliezer4Eduard Bokman5Alon Zaslaver6Department of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityDepartment of Genetics, Silberman Institute of Life Science, Edmond J. Safra Campus, The Hebrew UniversityAbstract Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatiotemporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in Caenorhabditis elegans animals can cell‐autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly changing continuous gradients. This encoding relies on a simple negative feedback in the G‐protein‐coupled receptor (GPCR) signaling pathway in which TAX‐6/Calcineurin plays a key role in mediating the feedback inhibition. This negative feedback supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient's first derivative. A simple mathematical model explains the fine neural dynamics of both wild‐type and tax‐6 mutant animals, further highlighting how the calcium‐dependent activity of TAX‐6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a general solution for efficient cell‐autonomous coding of external stimuli.https://doi.org/10.15252/msb.202110514calcineurin/TAX‐6calcium imagingGPCR signalingnegative feedbackpulsatile response |
| spellingShingle | Rotem Ruach Shai Yellinek Eyal Itskovits Noa Deshe Yifat Eliezer Eduard Bokman Alon Zaslaver A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli Molecular Systems Biology calcineurin/TAX‐6 calcium imaging GPCR signaling negative feedback pulsatile response |
| title | A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli |
| title_full | A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli |
| title_fullStr | A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli |
| title_full_unstemmed | A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli |
| title_short | A negative feedback loop in the GPCR pathway underlies efficient coding of external stimuli |
| title_sort | negative feedback loop in the gpcr pathway underlies efficient coding of external stimuli |
| topic | calcineurin/TAX‐6 calcium imaging GPCR signaling negative feedback pulsatile response |
| url | https://doi.org/10.15252/msb.202110514 |
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