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

• Main Authors: Vozdek, Roman (Author), Bhatla, Nikhil (Contributor), Ma, Dengke (Contributor), Horvitz, Howard Robert (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), McGovern Institute for Brain Research at MIT (Contributor), Horvitz, H. Robert (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2014-01-24T19:21:23Z.
• Subjects: Article
• Online Access: Get fulltext

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)