The C. elegans genome contains 27 transmembrane guanylyl cyclases (tmGCs), a relatively large repertoire compared to other sequenced metazoan genomes. Most of the cyclases show limited expression in a few neurons or tissue types (1,2). However,
gcy-28 is expressed in many tissues, including most neurons. Here we show that ODR-11/GCY-28 functions in chemotaxis to AWC-sensed odors and resistance to acute hypo-osmotic stress.
In a screen for chemotaxis mutants we isolated
odr-11(
ky713), which has a missense mutation in the conserved cyclase domain of the tmGC T01A4.1 (recently named
gcy-28). ODR-11 has cyclase activity in vitro, confirming its identity as a GC (3).
odr-11(
ky713) is defective in chemotaxis to odors sensed by AWC, but not to those sensed by AWA. The chemotaxis defect can be rescued by inducing expression of
odr-11 under a heat-shock promoter in adults.
odr-11 expression in neurons rescues chemotaxis, but AWC-specific expression of
odr-11 is not sufficient. Rather than playing a role in primary AWC transduction, ODR-11 may play a regulatory role in chemotaxis.
When C. elegans is exposed to a sudden large drop in external osmolarity, it becomes uncoordinated and reduces speed of locomotion. The effect of hypo-osmotic stress is dose-dependent and either NaCl or sucrose can be used to alter the osmolarity. In
odr-11(
ky713) mutants this effect is enhanced and a large fraction of animals becomes transiently paralyzed after hypo-osmotic shock. Expression of
odr-11 in neurons, but not in body-wall muscles, rescues the mutant phenotype. An extracellular domain deletion of
odr-11 also rescues the hypo-osmotic stress defect in
odr-11(
ky713) mutants. However, this construct does not rescue the chemotaxis defect.
Among the C.elegans tmGCs, ODR-11 is most homologous to the mammalian atrial natriuretic peptide (ANP) receptor (GCA). The ANP/GCA system functions in fluid homeostasis (4). GCA knockout mice have chronic hypertension, and GCA is required to prevent hypertension after acute volume overload. Because the C. elegans body is permeable to water, a change in its external osmolarity will lead to changes in internal fluid balance. We speculate that ODR-11 is a functional homolog of mammalian GCA and that understanding the role of ODR-11 in chemotaxis may give us insight into the in vivo role of GCA in regulating behavior.