Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans
| Autor: | Elaine K. Round, Alexander Gottschalk, Shuo Luo, Timothy R. Mahoney, Martin Brauner, Michael L. Nonet, James H. Thomas |
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| Rok vydání: | 2008 |
| Předmět: |
Nervous system
Light Molecular Sequence Data Nerve Tissue Proteins gamma-Aminobutyric acid Synapse medicine Animals Intestinal Mucosa Caenorhabditis elegans gamma-Aminobutyric Acid G protein-coupled receptor Neurons Multidisciplinary Behavior Animal biology SNAP25 Biological Sciences biology.organism_classification Cell biology medicine.anatomical_structure Gene Expression Regulation Biochemistry Mutation GABAergic Signal transduction SNARE Proteins Locomotion Signal Transduction medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:16350-16355 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0803617105 |
| Popis: | The Caenorhabditis elegans defecation motor program (DMP) is a highly coordinated rhythmic behavior that requires two GABAergic neurons that synapse onto the enteric muscles. One class of DMP mutants, called anterior body wall muscle contraction and expulsion defective ( aex ) mutants, exhibits similar defects to those caused by the loss of these two neurons. Here, we demonstrate that aex-2 encodes a G-protein–coupled receptor (GPCR) and aex-4 encodes an exocytic SNAP25 homologue. We found that aex-2 functions in the nervous system and activates a G s α signaling pathway to regulate defecation. aex-4 , on the other hand, functions in the intestinal epithelial cells. Furthermore, we show that aex-5 , which encodes a pro-protein convertase, functions in the intestine to regulate the DMP and that its secretion from the intestine is impaired in aex-4 mutants. Activation of the G s α GPCR pathway in GABAergic neurons can suppress the defecation defect of the intestinal mutants aex-4 and aex-5 . Lastly, we demonstrate that activation of GABAergic neurons using the light-gated cation channel channelrhodopsin-2 is sufficient to suppress the behavioral defects of aex-2 , aex-4 , and aex-5 . These results genetically place intestinal genes aex-4 and aex-5 upstream of GABAergic GPCR signaling. We propose a model whereby the intestinal genes aex-4 and aex-5 control the DMP by regulating the secretion of a signal, which activates the neuronal receptor aex-2 . |
| Databáze: | OpenAIRE |
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