Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium
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- Trese Leinders-Zufall
- *Department of Physiology, University of Saarland School of Medicine, 66421 Homburg/Saar, Germany;
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- Renee E. Cockerham
- Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Stylianos Michalakis
- Munich Center for Integrated Protein Science and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany;
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- Martin Biel
- Munich Center for Integrated Protein Science and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 Munich, Germany;
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- David L. Garbers
- Department of Pharmacology and the Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390; and
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- Randall R. Reed
- Department of Molecular Biology and Genetics and Center for Sensory Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205
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- Frank Zufall
- *Department of Physiology, University of Saarland School of Medicine, 66421 Homburg/Saar, Germany;
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- Steven D. Munger
- Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201;
抄録
<jats:p> 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 <jats:italic>Gucy2d</jats:italic> , which encodes GC-D, with patch clamp recording and confocal Ca <jats:sup>2+</jats:sup> imaging from single dendritic knobs <jats:italic>in situ</jats:italic> , 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 Ca <jats:sup>2+</jats:sup> and action potential firing. Responses are eliminated in both <jats:italic>Gucy2d</jats:italic> - and <jats:italic>Cnga3</jats:italic> -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. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 104 (36), 14507-14512, 2007-09-04
Proceedings of the National Academy of Sciences