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
Author(s)
Vozdek, Roman; Bhatla, Nikhil; Ma, Dengke; Horvitz, Howard Robert
DownloadHorvitz_CYSL-1 interacts.pdf (2.244Mb)
PUBLISHER_POLICY
Publisher Policy
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.
Terms of use
Metadata
Show full item recordAbstract
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.
Date issued
2012-03Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MITJournal
Neuron
Publisher
Elsevier
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.
Version: Final published version
ISSN
08966273
1097-4199