dc.contributor.author | Vozdek, Roman | |
dc.contributor.author | Bhatla, Nikhil | |
dc.contributor.author | Ma, Dengke | |
dc.contributor.author | Horvitz, Howard Robert | |
dc.date.accessioned | 2014-01-24T19:21:23Z | |
dc.date.available | 2014-01-24T19:21:23Z | |
dc.date.issued | 2012-03 | |
dc.date.submitted | 2011-12 | |
dc.identifier.issn | 08966273 | |
dc.identifier.issn | 1097-4199 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/84512 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant GM24663) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.). Graduate Research Fellowship Program | en_US |
dc.description.sponsorship | Helen Hay Whitney Foundation (Postdoctoral Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.neuron.2011.12.037 | en_US |
dc.rights | 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. | en_US |
dc.source | Elsevier Open Archive | en_US |
dc.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 | en_US |
dc.type | Article | en_US |
dc.identifier.citation | 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. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences | en_US |
dc.contributor.department | McGovern Institute for Brain Research at MIT | en_US |
dc.contributor.mitauthor | Ma, Dengke | en_US |
dc.contributor.mitauthor | Bhatla, Nikhil | en_US |
dc.contributor.mitauthor | Horvitz, H. Robert | en_US |
dc.relation.journal | Neuron | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Ma, Dengke K.; Vozdek, Roman; Bhatla, Nikhil; Horvitz, H. Robert | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9964-9613 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1693-4524 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |