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...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
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 |
| Summary: | 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. |
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