The body cavity neurons AQR, PQR and URX have been proposed to monitor the contents of the C. elegans body fluid1. These neurons express five atypical soluble guanylate cyclases (sGCs) called GCY-32, 34, 35, 36 and 372-4]. The haem group of GCY-35 binds oxygen (O2), suggesting that it can act as an O2 sensor4. Mutants lacking this gene show defects in aggregation behaviour and oxygen responses3-4. Like
gcy-35 mutants, animals lacking
gcy-36 exhibit defects in aggregation, aerotaxis and aerokinesis (3 & see abstract by Cheung et al). Mammalian sGCs function as ?/? heterodimers. We have shown that GCY-35 and GCY-36 act as ? and ? subunits respectively3. Together these data suggest that GCY-35/GCY-36 function as heterodimers. To ask if GCY-35/GCY-36 are sufficient to program O2 sensation in vivo, we targeted their expression to the AWB olfactory neurons. AWB mediates avoidance of repellant odors by regulating a cGMP-gated cation channel5. Consistent with our hypothesis, transgenic animals showed much stronger avoidance of high ambient O2 than controls. We next investigated the function of
gcy-32 and
gcy-34. Animals lacking these genes showed weak or no phenotypes in aggregation, aerotaxis and aerokinesis assays under standard cultivation conditions. This prompted us to investigate if these sGCs have more important functions when animals are grown under different conditions. To test this, we cultivated
npr-1 animals under hypoxic conditions. This treatment resulted in prolonged inhibition of aggregation behavior when animals were returned to normoxia. Moreover, whereas animals reared in normoxia strongly avoid low O2 tensions of 0 5%4, animals cultivated in hypoxia preferentially sought these low O2 tensions. This shift in aerotaxis was dependent on the length of hypoxia exposure, was reversible, and was influenced by the genotype at the
npr-1 locus. The shift in aerotaxis was observed only when hypoxia was associated with abundant food, suggesting that the reprogramming resulted from an association between low ambient O2 and favorable growth conditions. Strikingly, the loss of
gcy-32 and
gcy-34 disrupted the shift in O2 preference of hypoxia-cultivated worms. Our data suggest a model in which chronic activation of the AQR, PQR and URX neurons in response to low O2 activates GCY-32 and GCY-34 containing oxygen-sensors. This change in the functional state of GCY-32 and GCY-34 enables aerotaxis to low O2 environments and may provide a memory of previous cultivation in low O2. 1.Coates and de Bono, 2002 2.Yu et al. 1997 3.Cheung, et al. 2004. 4.Gray, et al. 2004 5.Troemel, et al. 1997.