Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans.

Thermosensation is critical for optimal regulation of physiology and behavior. C. elegans acclimates to its cultivation temperature (Tc) and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons, which are extraordinarily thermosensitive and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. We show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse cell types. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C. elegans provides insight into mechanisms of thermosensation and thermal acclimation and suggests that rGCs may represent a new family of molecular thermosensors.This work was funded in part by the NIH (R01 GM081639 and P01 GM103770 – P.S., T32007292 – V.M.H. and P01NS079419 - T.O.).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.neuron.2016.03.00

Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide <it>in vitro </it>have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode <it>C. elegans</it>. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested.</p> <p>Results</p> <p>We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (<it>ser-4, mod-1</it>), but not in the 5-HT transporter (<it>mod-5</it>) or synthesis (<it>tph-1</it>) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor <it>mod-1 </it>and dopamine defective <it>cat-2 </it>mutants, but only partially blocked in <it>ser-4 </it>mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic <it>C. elegans </it>strain that constitutively expresses Aβ, and bilobalide did not significantly affect this inhibition.</p> <p>Conclusion</p> <p>These results suggest that bilobalide may modulate specific 5-HT receptor subtypes, which involves interplay with dopamine transmission. Additional studies for the function of bilobalide in neurotransmitter systems could aid in our understanding of its neuroprotective properties.</p