Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium.
The mammalian main olfactory epithelium (MOE) recognizes and transduces olfactory cues through a G protein-coupled, cAMP-dependent signaling cascade. Additional chemosensory transduction mechanisms have been suggested but remain controversial. We show that a subset of MOE neurons expressing the orphan receptor guanylyl cyclase GC-D and the cyclic nucleotide-gated channel subunit CNGA3 employ an excitatory cGMP-dependent transduction mechanism for chemodetection. By combining gene targeting of Gucy2d, which encodes GC-D, with patch clamp recording and confocal Ca2+ imaging from single dendritic knobs in situ, we find that GC-D cells recognize the peptide hormones uroguanylin and guanylin as well as natural urine stimuli. These molecules stimulate an excitatory, cGMP-dependent signaling cascade that increases intracellular Ca2+ and action potential firing. Responses are eliminated in both Gucy2d- and Cnga3-null mice, demonstrating the essential role of GC-D and CNGA3 in the transduction of these molecules. The sensitive and selective detection of two important natriuretic peptides by the GC-D neurons suggests the possibility that these cells contribute to the maintenance of salt and water homeostasis or the detection of cues related to hunger, satiety, or thirst.
Leinders-Zufall
Trese
T
Department of Physiology, University of Saarland School of Medicine, 66421 Homburg/Saar, Germany.
Cockerham
Renee E
RE
Michalakis
Stylianos
S
Biel
Martin
M
Garbers
David L
DL
Reed
Randall R
RR
Zufall
Frank
F
Munger
Steven D
SD
D000595:Amino Acid Sequence; D000818:Animals; D004594:Electrophysiology; D004848:Epithelium / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D009831:Olfactory Mucosa / Q000201:enzymology* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D050705:Receptors, Guanylate Cyclase-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D008024:Ligands; D045265:Natriuretic Peptides; C084362:uroguanylin; D050705:Receptors, Guanylate Cyclase-Coupled