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
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Horvitz_CYSL-1 interacts.pdf
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Author(s)
Vozdek, Roman
Bhatla, Nikhil
Ma, Dengke
Horvitz, Howard Robert
Date Issued
March 2012
Journal
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2011.12.037
