Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans
A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a ge...
| Principais autores: | , , , , |
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| Formato: | Artigo |
| Idioma: | en_US |
| Publicado em: |
Genetics Society of America, The
2014
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| Acesso em linha: | http://hdl.handle.net/1721.1/85982 https://orcid.org/0000-0002-9964-9613 |
| _version_ | 1826188984490917888 |
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| author | Gustafson, Megan A. Gurel, Guliz Pepper, Judy S. Koelle, Michael R. Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gustafson, Megan A. Gurel, Guliz Pepper, Judy S. Koelle, Michael R. Horvitz, Howard Robert |
| author_sort | Gustafson, Megan A. |
| collection | MIT |
| description | A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. |
| first_indexed | 2024-09-23T08:07:43Z |
| format | Article |
| id | mit-1721.1/85982 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:07:43Z |
| publishDate | 2014 |
| publisher | Genetics Society of America, The |
| record_format | dspace |
| spelling | mit-1721.1/859822022-09-30T07:43:34Z Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans Gustafson, Megan A. Gurel, Guliz Pepper, Judy S. Koelle, Michael R. Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Horvitz, H. Robert Gustafson, Megan A. Horvitz, H. Robert A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. National Institutes of Health (U.S.) (Grant GM24663) 2014-04-03T13:56:24Z 2014-04-03T13:56:24Z 2012-09 2012-05 Article http://purl.org/eprint/type/JournalArticle 0016-6731 http://hdl.handle.net/1721.1/85982 Gurel, G., M. A. Gustafson, J. S. Pepper, H. R. Horvitz, and M. R. Koelle. “Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis Elegans.” Genetics 192, no. 4 (December 1, 2012): 1359–1371. https://orcid.org/0000-0002-9964-9613 en_US http://dx.doi.org/10.1534/genetics.112.142125 Genetics Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Genetics Society of America, The Horvitz via Courtney Crummett |
| spellingShingle | Gustafson, Megan A. Gurel, Guliz Pepper, Judy S. Koelle, Michael R. Horvitz, Howard Robert Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title | Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title_full | Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title_fullStr | Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title_full_unstemmed | Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title_short | Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans |
| title_sort | receptors and other signaling proteins required for serotonin control of locomotion in caenorhabditis elegans |
| url | http://hdl.handle.net/1721.1/85982 https://orcid.org/0000-0002-9964-9613 |
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