Imagine sitting in a room where the oxygen is slowly drained out; your first reaction would be to get up and leave as fast as possible. Indeed, an organism's first line of defence when faced with sudden fluctuations in environmental conditions is the hard-wired behavioral response that makes it seek better surroundings. But, what are the sensors in the brain that trigger these behavioral responses? The group of Cornelia Bargmann tackled this fundamental biological question by examining how the model organism, C. elegans, senses oxygen in its environment.

Oxygen-sensing is an important feature of most life forms on this planet. Too little oxygen imposes restrictions on the range of tasks an organism can perform; while too much oxygen can have deleterious physiological consequences due to the production of toxic reactive oxygen species.

To study the behavior of the 1 mm worm, the team devised a miniature oxygen-gradient chamber with a surface of 5 cm2. The animals avoided oxygen concentrations less than 2% and higher than 12%. With this information in hand, Jesse Gray and the rest of Bargmann's team focused their effort on understanding how the worms avoid high oxygen concentrations.

Cyclic GMP (cGMP) is known to play an important role in oxygen-sensing in Drosophila. cGMP is generated from GTP by guanylate cyclases (sGCs)and all guanylate cyclases identified to date are activated by nitric oxide. However, C. elegans seems to lack the enzymes necessary to synthesize nitric oxide, so the team hypothesized that C. elegans guanylate cyclases may be activated by oxygen, instead of nitric oxide, to play a role in oxygen sensing.

The first clue that guanylate cyclases in C. elegans could be responsible for oxygen-sensing was that these enzymes are expressed in cells that have a similar morphology to sensory neurons. The team then focused their study on one specific guanylate cyclase, GCY-35. To examine oxygen-sensing behavior in the absence of gcy-35, the group used mutant nematodes in which GCY-35 no longer produced cGMP. The gcy-35 mutants displayed normal hypoxia avoidance, but in contrast to wild-type animals they could not avoid hyperoxia. Similarly, animals that had mutations in the cGMP gated sensory transduction channel were unable to avoid hyperoxic conditions. Since this channel is expressed in the same sensory neurons as GCY-35, it suggests that an oxygen-sensing mechanism through GCY-35 is triggered by cGMP. Importantly, the team showed that the haem domain of GCY-35 displays oxygen-binding characteristics similar to haemoglobin. Together, these results show that GCY-35 acts an oxygen sensor in C. elegans.

The group went on to show an even more surprising result, namely that oxygen sensing influences feeding behavior. Laboratory strains of C. elegans are normally kept on agar plates seeded with a bacterial lawn for food. The bacterial lawn naturally creates its own oxygen gradient: the center of the lawn has higher oxygen levels than the thick border. Each C. elegans strain has a tendency to aggregate while feeding and to accumulate at the outer border of the lawn, probably to avoid elevated oxygen concentrations. However, the gcy-35 mutants aggregated and occupied the borders less than wild-type animals. In addition, the feeding behavior of the mutants was unaffected by oxygen concentration contrary to the wild-type animals, which occupied the borders at elevated oxygen concentration but not at low oxygen levels. Therefore, oxygen acts through GCY-35 to regulate social feeding.

This work promises to be a significant stepping-stone for comparative physiologists working to understand oxygen-sensing at various levels on the evolutionary scale.

References

Gray, J. M., Karow, D. S., Lu, H., Chang, A. J., Chang, J. S.,Ellis, R. E., Marletta, M. A. and Bargmann, C. I. (
2004
). Oxygen sensation and social feeding mediated by a C. elegansguanylate cyclase homologue.
Nature
430
,
317
-322.