Oxygen (O2) is essential for the growth and development nearly all metazoans. O2 concentrations in the environment fluctuate and C. elegans exhibits an aerotaxis behavior dependent on the activity of soluble guanylate cylcases,
npr-1 and
glb-5. We show that, in addition to the previously described aerotaxis pathway, C. elegans displays a genetically distinct acute hypoxia avoidance response (HAR). When worms are placed in hypoxic atmospheres containing less than 5% O2 they immediately switch from a dwelling to roaming behavior. Roaming speed is inversely correlated with %O2 down to 1% O2 and is positively correlated with O2 concentrations <1%.
In addition to its requirement for oxidative phosphorylation, molecular O2 is required for the synthesis of the monoamine neurotransmitters which regulate the switch from dwelling to roaming behaviors. The inhibition of roaming by monoamine neurotransmitters requires the activity of the heterotrimeric G-protein GOA-1. We find that loss of function mutations in
goa-1 eliminate HAR.
goa-1 animals also display a premature entry into suspended animation (SA) at O2 concentrations 0.1%. GOA-1 negatively regulates the activity of the PLC-b EGL-8 through EGL-30.
egl-8 animals display a severely attenuated HAR and also prematurely enter SA. EGL-8 signaling through diacylglycerol (DAG) is negatively regulated by the DAG kinase DGK-1. In moderate hypoxia (³5% O2)
dgk-1 worms, like
npr-1 worms, show a pronounced decrease in locomotion. However, unlike
npr-1 worms, at < 5% O2,
dgk-1 worms show an inverse HAR; locomotion is increased in room air but suppressed in hypoxia.
Hypoxia survival in C. elegans and other metazoans requires the transcription factor HIF-1.
hif-1 loss of function animals show no defects in HAR, however, animals that lack the function of the prolylhydroxylase EGL-9, the negative regulator of HIF-1, show an immediate arrest of locomotion when transferred to hypoxia. This arrest is transient and
egl-9 animals slowly increase speed during hypoxia eventually reaching wildtype levels of locomotion. Because
dgk-1 worms show a similar arrest immediately upon transition to hypoxia, we tested the affect of hypoxia on embryonic diapause, a phenotype which requires HIF-1. We found that
dgk-1 worms, like
hif-1 worms, exhibit a precocious diapause at 0.5% O2. This suggests that the GOA-1/DGK-1 pathway might influence HIF-1.