None yet reported, although described to have gap junctions in adult animals (MoW)
- GCY-1; transmembrane receptor guanylate cyclase
- GCY-25; transmembrane receptor guanylate cyclase
- GCY-32; soluble guanylate cyclase
- GCY-34; soluble guanylate cyclase
- GCY-35; soluble guanylate cyclase, binds molecular oxygen and mediates oxygen sensation. Heterodimerizes with GCY-36
- GCY-36; soluble guanylate cyclase
- GCY-37; soluble guanylate cyclase
- NPR-1; receptor for flp-18- and flp-21-encoded peptides
- PDFR-1; pigment dispersing factor (PDF-1) receptor
- SRA-10; G protein-coupled seven transmembrane receptor
(Wormbase; Barrios et al., 2012; Cheung et al., 2004; Gray et al., 2004; Troemel et al., 1995)
- Functions in aerotaxis: When placed in an O2 gradient, C. elegans shows a strong behavioral preference for ~5–10% (intermediate) O2 levels and avoids both hypoxia (<7%) and hyperoxia (21%). Animals navigate the O2 gradients by O2-induced changes in locomotion speed, reversal and turning behavior (Cheung et al., 2005; Gray et al., 2004). This preference for intermediate O2 levels (Gray et al., 2004), may work to allow oxidative metabolism but avoid oxidative stress (Lee and Atkinson, 1977). The intermediate O2 preference also promotes aggregation behavior, possibly since aggregating C. elegans locally deplete O2 to preferred levels (Gray et al., 2004; Rogers et al., 2006). The rise in O2 levels detected by animals leaving a group induces reversal (backing) and turning. Conversely, the fall in O2 encountered when entering a group suppresses reversal, turning, and rapid locomotion, allowing the animal to stay with the group. Soluble guanylate cyclase (sGC)-expressing, oxygen-sensing neurons (URX, BAG, AQR, PQR, SDQ, BDU, ALN, and PLN) mediate the responses to ambient O2 levels (Zimmer et al, 2009). For aggregation, URX appears to be the most important member of this group (Coates and de Bono, 2002), while for aerotactic behavior in an O2 gradient, URX is redundant with other sGC-expressing neurons (Chang et al., 2006). O2 sensation mainly requires the opposing actions of BAG and URX sensory neurons; in wild type animals with high NPR-1 function, BAG neurons sense drops in O2 concentrations, while URX neurons sense elevations. The interaction of these neurons results in locomotion responses allowing the worm to find and settle at places of preferred O2 concentrations. The O2-sensing abilities of BAG and URX neurons are attributed to specific O2-binding sGCs within those neuron classes (GCY-31 and GCY-33 in BAG neurons, and GCY-35 and GCY-36 in URX neurons) (Skora and Zimmer, 2013; Zimmer et al, 2009).
The locations of URX in the head and PQR in the tail facilitate high O2 avoidance by the animal accelerating forward without changing direction of movement when its tail/PQR encounters high O2 and by reversal and turning when its head/URX encounters high O2 (Busch et al., 2012). Two post-synaptic targets of URX, AUA and RMG, seem to be involved in this O2-induced behavioral response.
The strength of the O2 response is regulated by food, genotype, and an animal’s prior O2 exposure. The lab standard wild-type C. elegans strain (N2) with high activity of the neuropeptide receptor NPR-1 (215V) is indifferent to high O2 when food is present, whereas C. elegans isolates with low activity of NPR-1 (215F) avoid high O2 in the presence of food, and therefore, aggregate (Gray et al., 2004; Rogers et al., 2006). Since all strains avoid high O2 when food is absent, NPR-1 may be an internal food sensor important for food-related regulation of aggregation (i.e., regulation of social behavior on food) (Chang et al., 2006). Also other studies indicate that animals that carry the npr-1 (215F) allele or that lack npr-1 function tend to dwell (slow down) in low ambient O2 and roam (disperse) in high ambient O2. In this model, in animals with low NPR-1 activity, drops in O2 lead to increased activity of a GCY-35/36 heterodimeric soluble guanylate cyclase. Rising cGMP, in turn, opens the TAX-2/TAX-4 cGMP-gated ion channel in AQR, PQR and URX leading to their depolarization and when the food is present, strong suppression of roaming behavior (Cheung et al., 2005).
Cultivation conditions also regulate O2 preference: animals cultivated in hypoxia migrate to lower O2 levels, and avoid high O2 regardless of food or NPR-1 genotype (Cheung et al., 2005; Chang and Bargmann, 2008). The sensory neurons ASH, ADL, and ADF also promote avoidance of high O2 levels (through function of TRP-related channel subunits OCR-2 and OSM-9 and the transmembrane protein ODR-4 in nociceptive ASH and ADL, and serotonin production by ADF), but these cells are not needed after animals are cultivated in hypoxia (Chang et al., 2006; Chang and Bargmann; 2008; Rogers et al., 2006).
- AQR, PQR and URX are weak CO2-sensors and contribute to CO2 avoidance (main CO2 sensors are AFD, BAG and ASE)(Bretscher et al., 2011).
- Lifespan regulation; ablation of low-O2-sensing BAG neurons increases lifespan, while ablation of high-O2-sensing URX neurons decreases lifespan. BAG and URX neurons counterbalance each other for control of lifespan via functions of different sCGs. Also, their life-span modulating effects are independent of canonical life-span modulatory pathways, including DAF-2/DAF-16, DAF-12, germline signaling, sensory perception pathways or dietary restriction (Liu and Cai; 2013)
- AQR, PQR and URX suppress innate immunity via NPR-1, which regulates both PMK-1-dependent and PMK-1-independent immune responses (Styer et al., 2008). Since URX, AQR, PQR are exposed to pseudocoelomic fluid, they are hypothesized to communicate neuroendocrine signals to nonneural tissues involved in innate immunity defense responses.