CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans
The C. elegans HIF-1 proline hydroxylase EGL-9 functions as an O[subscript 2] sensor in an evolutionarily conserved pathway for adaptation to hypoxia. H[subscript 2]S accumulates during hypoxia and promotes HIF-1 activity, but how H[subscript 2]S signals are perceived and transmitted to modulate HIF...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84512 https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0002-1693-4524 |
| _version_ | 1811076476480520192 |
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| author | Vozdek, Roman Bhatla, Nikhil Ma, Dengke Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Vozdek, Roman Bhatla, Nikhil Ma, Dengke Horvitz, Howard Robert |
| author_sort | Vozdek, Roman |
| collection | MIT |
| description | The C. elegans HIF-1 proline hydroxylase EGL-9 functions as an O[subscript 2] sensor in an evolutionarily conserved pathway for adaptation to hypoxia. H[subscript 2]S accumulates during hypoxia and promotes HIF-1 activity, but how H[subscript 2]S signals are perceived and transmitted to modulate HIF-1 and animal behavior is unknown. We report that the experience of hypoxia modifies a C. elegans locomotive behavioral response to O[subscript 2] through the EGL-9 pathway. From genetic screens to identify novel regulators of EGL-9-mediated behavioral plasticity, we isolated mutations of the gene cysl-1, which encodes a C. elegans homolog of sulfhydrylases/cysteine synthases. Hypoxia-dependent behavioral modulation and H[subscript 2]S-induced HIF-1 activation require the direct physical interaction of CYSL-1 with the EGL-9 C terminus. Sequestration of EGL-9 by CYSL-1 and inhibition of EGL-9-mediated hydroxylation by hypoxia together promote neuronal HIF-1 activation to modulate behavior. These findings demonstrate that CYSL-1 acts to transduce signals from H[subscript 2]S to EGL-9 to regulate O[subscript 2]-dependent behavioral plasticity in C. elegans. |
| first_indexed | 2024-09-23T10:22:46Z |
| format | Article |
| id | mit-1721.1/84512 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:22:46Z |
| publishDate | 2014 |
| publisher | Elsevier |
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| spelling | mit-1721.1/845122022-09-26T17:30:45Z CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans Vozdek, Roman Bhatla, Nikhil Ma, Dengke Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Ma, Dengke Bhatla, Nikhil Horvitz, H. Robert The C. elegans HIF-1 proline hydroxylase EGL-9 functions as an O[subscript 2] sensor in an evolutionarily conserved pathway for adaptation to hypoxia. H[subscript 2]S accumulates during hypoxia and promotes HIF-1 activity, but how H[subscript 2]S signals are perceived and transmitted to modulate HIF-1 and animal behavior is unknown. We report that the experience of hypoxia modifies a C. elegans locomotive behavioral response to O[subscript 2] through the EGL-9 pathway. From genetic screens to identify novel regulators of EGL-9-mediated behavioral plasticity, we isolated mutations of the gene cysl-1, which encodes a C. elegans homolog of sulfhydrylases/cysteine synthases. Hypoxia-dependent behavioral modulation and H[subscript 2]S-induced HIF-1 activation require the direct physical interaction of CYSL-1 with the EGL-9 C terminus. Sequestration of EGL-9 by CYSL-1 and inhibition of EGL-9-mediated hydroxylation by hypoxia together promote neuronal HIF-1 activation to modulate behavior. These findings demonstrate that CYSL-1 acts to transduce signals from H[subscript 2]S to EGL-9 to regulate O[subscript 2]-dependent behavioral plasticity in C. elegans. National Institutes of Health (U.S.) (Grant GM24663) National Science Foundation (U.S.). Graduate Research Fellowship Program Helen Hay Whitney Foundation (Postdoctoral Fellowship) 2014-01-24T19:21:23Z 2014-01-24T19:21:23Z 2012-03 2011-12 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/84512 Ma, Dengke K., Roman Vozdek, Nikhil Bhatla, and H. Robert Horvitz. “CYSL-1 Interacts with the O2-Sensing Hydroxylase EGL-9 to Promote H2S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans.” Neuron 73, no. 5 (March 2012): 925-940. Copyright © 2012 Elsevier Inc. https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0002-1693-4524 en_US http://dx.doi.org/10.1016/j.neuron.2011.12.037 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Vozdek, Roman Bhatla, Nikhil Ma, Dengke Horvitz, Howard Robert CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title | CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title_full | CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title_fullStr | CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title_full_unstemmed | CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title_short | CYSL-1 Interacts with the O[subscript 2]-Sensing Hydroxylase EGL-9 to Promote H[subscript 2]S-Modulated Hypoxia-Induced Behavioral Plasticity in C. elegans |
| title_sort | cysl 1 interacts with the o subscript 2 sensing hydroxylase egl 9 to promote h subscript 2 s modulated hypoxia induced behavioral plasticity in c elegans |
| url | http://hdl.handle.net/1721.1/84512 https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0002-1693-4524 |
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