A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway

Juilfs, Dawn M.; Fülle, Hans-Jürgen; Zhao, Allan Z.; Houslay, Miles D.; Garbers, David L.; Beavo, Joseph A.

doi:10.1073/pnas.94.7.3388

Cited by 289 publications

(335 citation statements)

References 37 publications

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“…6C). The expression of two other markers of GC-D neurons, PDE2 (18) and CNGA3 (17), was unaffected. Only a small subset of MOE neurons in Gucy2d ϩ/Ϫ and Ϫ/Ϫ mice express the ␤-galactosidase (␤-gal) reporter (SI Fig.…”

Section: Targeting Of Gc-d Neurons and The Necklace Glomeruli In Micementioning

confidence: 90%

“…Although these cells were identified more than a decade ago (16), there is no functional evidence that they play a role in odor recognition. On the basis of their distinct molecular profiles and axonal targets in the olfactory bulb (OB) (16)(17)(18), GC-D cells have been suggested to respond to hormones or pheromones (18). However, it has not been possible to obtain physiological recordings from identified GC-D neurons.…”

mentioning

confidence: 99%

“…GC-D cells lack key components of the canonical OSN odor transduction cascade, including G␣ olf , type III adenylyl cyclase, the Ca 2ϩ /calmodulin-dependent phosphodiesterase PDE1C2, the cAMP-specific phosphodiesterase PDE4A, and the cAMPsensitive CNG channel subunits CNGA2 and CNGB1b (17,18). Instead, these neurons express a cGMP-specific CNG channel subunit, CNGA3, and a cGMP-stimulated phosphodiesterase, PDE2 (17,18). Although these cells were identified more than a decade ago (16), there is no functional evidence that they play a role in odor recognition.…”

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confidence: 99%

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Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

Leinders‐Zufall

Cockerham

Michalakis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian main olfactory epithelium (MOE) recognizes and transduces olfactory cues through a G protein-coupled, cAMPdependent 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 Ca 2؉ 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 Ca 2؉ 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.O dor recognition by canonical olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE) begins when odor molecules bind to any one of many hundred G protein-coupled odorant receptors (1-4). Upon ligand binding, odorant receptors activate the G protein G␣ olf , which stimulates type III adenylyl cyclase to increase intracellular levels of cAMP (4-9). This second messenger then directly opens cAMPsensitive, cyclic nucleotide-gated (CNG) channels in the plasma membrane, resulting in the initial depolarization of the cell (3, 4). OSNs that use this cAMP-mediated transduction cascade respond to a wide variety of odors, including food odors, volatile pheromones, and peptides that bind major histocompatibility complex proteins (4, 10-12). A recently discovered second family of G protein-coupled receptors expressed in the MOE, the trace amine-associated receptors, may also function in the recognition of some odors or pheromones by coupling to the canonical cAMP pathway (13). However, there has been intense debate as to whether the cAMP cascade is the only excitatory sensory transduction mechanism in the MOE (11,14,15).A subpopulation of ciliated MOE neurons that express the orphan receptor guanylyl cyclase GC-D (16) are prime candidates to mediate cAMP-independent odor recognition. GC-D cells lack key components of the canonical OSN odor transduction cascade, including G␣ olf , type III adenylyl cyclase, the Ca 2ϩ /calmodulin-dependent phosphodiesterase PDE1C2, the cAMP-specific phosphodiesterase PDE4A, and the cAMPsensitive CNG channel subunits CNGA2 and CNGB1b (17,18). Instead, these neurons express a cGMP-specific CNG channel subunit, CNGA3, and a cGMP-stimulated phosphodiesterase, PDE2 (17,18). Although these cells were identified more than a de...

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Section: Targeting Of Gc-d Neurons and The Necklace Glomeruli In Micementioning

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

Leinders‐Zufall

Cockerham

Michalakis

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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198

267

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“…This subset of neurons also appears to innervate atypical glomeruli in the olfactory bulb known as necklace glomeruli [82,204]. Only the necklace glomeruli express tyrosine hydroxylase reflecting afferent activities in mice lacking OCNC1, a subunit of the OCNC [206].…”

Section: J Other Single Transmembrane Segment Formsmentioning

confidence: 99%

“…A subset of olfactory neurons selectively expresses a cGMP-stimulated PDE (PDE2), GC-D, and a subunit of a cGMP-gated channel identified in cone photoreceptors, while they do not show detectable expression of players known to be important in odorant sensing in other olfactory neurons, Golf, type III adenylyl cyclase, and the olfactory cyclic nucleotide-gated channel (OCNC) [82,204,205]. This subset of neurons also appears to innervate atypical glomeruli in the olfactory bulb known as necklace glomeruli [82,204].…”

Section: J Other Single Transmembrane Segment Formsmentioning

confidence: 99%

The Regulation and Physiological Roles of the Guanylyl Cyclase Receptors.

2001

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Immunohistochemical identification of discrete subsets of rat olfactory neurons and the glomeruli that they innervate

1997

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Glomeruli at the posterior margin of the main olfactory bulb differ in several respects from those located in the remainder of the bulb; e.g., the olfactory sensory neurons (OSNs) that project here exhibit a distinct biochemical phenotype and signal transduction pathway, the microcircuitry of the glomeruli is substantially altered, and the glomeruli are activated by unconventional odorants. In the present work, we report that the monoclonal antibodies 2C6 and MAb213 label distinct subsets of OSNs in the olfactory epithelium (OE), including their axons to their terminations in the main olfactory bulb (MOB). Neurons immunopositive with 2C6 are concentrated in the cul-de-sacs of ectoturbinates 1 and 2 and of endoturbinate IV. Unlike the vast majority of OSNs, 2C6(+) neurons express olfactory marker protein (OMP) at a low level, but their failure to stain with anti-GAP-43 labeling indicates that the OMP "weak" neurons are nonetheless mature. Glomeruli positive for 2C6 are bilaterally symmetrical and occupy reproducible positions along the posterior margin of the MOB. Three of these are very large, and we refer to them as the lateral, posterior ventral, and anterior ventral 2C6(+) necklace glomeruli. MAb213(+) neurons are concentrated in the posteriormost tips of the cul-de-sacs and recesses at the reflection of the OE at the cribriform plate. Like 2C6(+) neurons, MAb213(+) OSNs are weakly labeled with anti-OMP but are fully mature. MAb213(+) glomeruli are also bilaterally symmetrical; they occupy reproducible positions along the posterior margin of the MOB. The three largest glomeruli occupy lateral, posterior ventral, and posterior positions; the first two are found close to the aforementioned 2C6(+) glomeruli. MAb213 also intensely labels one of the glomeruli of the modified glomerular complex, a string of small glomeruli ventrally, and another string dorsal to the accessory olfactory bulb. Acetylcholinesterase (AChE) histochemical staining of adjacent sections showed that many, but not all, MAb213(+) glomeruli colocalize with dense or moderate AChE staining. Thus, it is likely that the "necklace olfactory glomeruli" (Shinoda et al., 1990, 1993) and the phosphodiesterase (PDE2)(+) glomeruli (Juilfs et al., 1997) are a subset(s) of the MAb213(+) glomeruli. On the other hand, 2C6(+) glomeruli are not associated with AChE staining. These data indicate that the 2C6(+) glomeruli comprise a novel subset in the posterior MOB. In addition to the 2C6(+) and MAb213(+) necklace glomeruli, there is another distinct set of glomeruli at the posterior margin of the bulb that are OMP(-), 2C6(-), and MAb213(-). In summary, the current work indicates that glomeruli at the posterior margin of the bulb, which are necklace glomeruli in terms of location and appearance, are actually heterogeneous and may subserve specialized functions within the olfactory system.

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A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway

Cited by 289 publications

References 37 publications

Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

The Regulation and Physiological Roles of the Guanylyl Cyclase Receptors.

Immunohistochemical identification of discrete subsets of rat olfactory neurons and the glomeruli that they innervate

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