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  • Several lines of evidence suggest that thermosensation in AF


    Several lines of evidence suggest that thermosensation in AFD is unlikely to be mediated by thermosensitive ion channels. AFD exhibits a steep temperature dependence with a reported Q of >1015 for temperature-evoked current, implying a strong amplification step in the thermotransduction process (Ramot et al., 2008). Moreover, an ∼100-ms latency has been observed between changes in the temperature stimulus and evoked current, suggesting the involvement of a second messenger in thermosensory signaling (Ramot et al., 2008). Genetic and behavioral experiments suggest that this second messenger is cGMP. AFD neurons in animals mutant for AFD-specific receptor guanylyl cyclases (AFD-rGCs), or cGMP-gated channels, fail to respond to temperature changes, and these animals are behaviorally atactic on thermal gradients (Garrity et al., 2010). Based on these observations, we and others have proposed that warming increases and/or decreases the catalytic activity of rGCs or phosphodiesterases (PDEs), methane monooxygenase respectively, and that the resulting increase in intracellular cGMP activates cyclic nucleotide-gated channels to depolarize AFD (Garrity et al., 2010). However, whether rGCs or PDEs are themselves thermosensors or act downstream of other thermosensory proteins in AFD is unknown. Here we show that a set of AFD-rGCs is both necessary in AFD for thermosensation and sufficient to confer robust temperature responses upon expression in diverse non-thermosensory neuronal and non-neuronal cell types. The operating range of AFD-rGC-expressing cells is determined largely by the individual rGC and cell type, indicating that T-correlated methane monooxygenase of thermosensory response threshold is an AFD-specific property. We find that coexpression of AFD-rGCs can further shape temperature responses and that both the extracellular domain (ECD) and intracellular domain (ICD) of these rGCs are necessary for their thermosensitive properties. Identification of thermosensitive rGCs in C. elegans provides insight into the mechanisms by which neurons can achieve exceptional thermosensitivity, and together with the recently identified mouse receptor guanylyl cyclase G thermosensory molecule (Chao et al., 2015), may define a new family of evolutionarily conserved thermoreceptors.
    Discussion We have shown that AFD-rGCs are necessary in AFD, and sufficient when expressed in multiple non-thermosensory cell types, to confer highly sensitive temperature responses. Each AFD-rGC confers responses in a distinct temperature range in different cell types. Previous work indicated that is regulated by intracellular cGMP and calcium concentrations and appears to be a cell-intrinsic property (Ramot et al., 2008, Wang et al., 2013, Wasserman et al., 2011, Yu et al., 2014). We suggest that the distinct activation temperatures of AFD-rGCs are a consequence of the resting levels of intracellular cGMP and calcium in misexpressing cells and tissues. As in mammalian photoreceptors, intracellular calcium levels may be read out by calcium sensor proteins, such as guanylyl cyclase-activating proteins (GCAPs) (Lim et al., 2014, Sharma and Duda, 2012), to modulate rGC enzymatic activity in a cell-type-specific manner. Indeed, loss of function of the NCS-1 neuronal calcium sensor results in a higher (Wang et al., 2013) and altered thermotaxis behaviors (Gomez et al., 2001). is also highly flexible and is regulated by T experience via both transcription-dependent and -independent mechanisms (Yu et al., 2014). The absence of these mechanisms in misexpressing cells may partly underlie the weak T-dependent modulation of T∗ upon ectopic expression. We conclude that AFD-rGCs are instructive for thermosensation but that the activation temperature of individual AFD-rGCs is cell context-dependent. We and others have been unable to confer AFD-rGC-mediated temperature responses onto heterologous cells, in part due to defects in membrane trafficking of these proteins (D.A. Glauser and M.B. Goodman, personal communication; G. Budelli, Y.V.Y., A.T., and P.S., unpublished data); thus, it remains possible that additional factors contribute to their thermosensory functions.