title: Defining specificity determinants of cGMP mediated gustatory sensory transduction in Caenorhabditis elegans.
abstract: Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Heidi K
authors.initials: HK
authors.lastname: Smith
authors.forename: Linjiao
authors.initials: L
authors.lastname: Luo
authors.forename: Damien
authors.initials: D
authors.lastname: O'Halloran
authors.forename: Dagang
authors.initials: D
authors.lastname: Guo
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
authors.forename: Aravinthan D T
authors.initials: AD
authors.lastname: Samuel
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D006152:Cyclic GMP / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D012965:Sodium Chloride / Q000494:pharmacology; D013649:Taste / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; C102183:tax-2 protein, C elegans; C102184:tax-4 protein, C elegans; D012965:Sodium Chloride; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: C. elegans; gcy genes; gustation