Many of us crawl under the covers to hide from morning sunlight. Euglena gracilis is a single-celled flagellate that also avoids intense light. Its photo-avoidance behaviors require a photo-activated adenylate cyclase (PAC). Schröder-Lang et al. report light-induced behaviors in Drosophila expressing PAC in a recent article in Nature Methods.
Adenylate cyclase converts ATP to cyclic AMP (cAMP). Cylic AMP activates cAMP-dependent protein kinase and is degraded by phosphodiesterase. The authors expressed the two PAC subunits, a and 
, in Xenopus oocytes. They found similar concentrations of cAMP in PAC-expressing and wild-type oocytes. In contrast, PAC
-expressing oocytes showed a twenty-fold increase in cAMP concentrations relative to wild-type oocytes. Exposure to five minutes of blue light (approximately 480 nm) increased cAMP another ten-fold in PAC-expressing oocytes, but did not change cAMP in PAC-expressing oocytes.
cAMP-dependent protein kinase phosphorylates and activates a chloride channel, cystic fibrosis transmembrane conductance regulator. Blue light increased membrane conductance in oocytes expressing cystic fibrosis transmembrane conductance regulator and either PAC or PAC, suggesting that light initiated cAMP signaling in PAC-expressing oocytes. However, oocytes needed 100-fold more PAC relative to PAC complementary RNA to mount a response to blue light, suggesting that PAC is more potent than PAC.
Cyclic nucleotide-gated channels are ion channels that open in response to cyclic nucleotides, including cAMP. In oocytes co-expressing PAC and cyclic nucleotide-gated channels, current increased within 20 milliseconds of the onset and stopped several milliseconds after the conclusion of blue light irradiation, suggesting that activity in PAC-expressing cells could be temporally controlled with light.
Drosophila expressing PAC, but not PAC, showed freezing behavior and an unusual leg tremor while in the presence of blue light. The authors targeted PAC to the nervous system by breeding Drosophila expressing the yeast transcription factor Gal4 under the control of the neuron-specific elav promoter to Drosophila expressing PAC linked to the yeast upstream activating sequence. They covered Drosophila with a fine powder that induced grooming behaviors. Wild-type Drosophila groomed consistently during alternating one-minute periods of dim white and strong blue light illumination. In contrast, Drosophila with PAC targeted to the nervous system showed reduced grooming behaviors while illuminated by blue light which returned to normal within seconds of the blue light's termination.
Together, these data suggest that PACs can be used to induce molecular events in the whole animal. The authors suggest that different experimental models can benefit from PAC, which induces high basal levels of cAMP that increase in blue light, and PAC, which does not change basal levels of cAMP but increases cAMP only under certain conditions. They propose using PACs to study complex behaviors, like learning and memory, that rely on cAMP signaling.