Ultrastructural localization of olfactory transduction components: the G protein subunit Golfα and type III adenylyl cyclase

Menco, Bert Ph. M.; Bruch, Richard C.; Dau, Barbara; Danho, Waleed

doi:10.1016/0896-6273(92)90272-f

Cited by 112 publications

(61 citation statements)

References 69 publications

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“…In earlier studies, mean values for the cilia number per knob were 18 in the dog, seven in the sheep (Kavoi et al, 2010), and 17 in the bovine (Menco, 1978). As the receptors for odor binding are mainly located on the cilia of olfactory neurons (Getchell, 1986;Buck and Axel, 1991;Kinnamon and Getchell, 1991;Menco et al, 1992Menco et al, , 1997Lowe and Gold, 1993;Liberles and Buck, 2006), it can be argued that the number of cilia per olfactory cell knob is reminiscent of the olfactory functional capability of a particular species.…”

Section: Postnatal Morphology Of Olfactory Mucosa In Rabbitsmentioning

confidence: 99%

Morphofunctional Adaptations of the Olfactory Mucosa in Postnatally Developing Rabbits

Kavoi

Makanya

Plendl

et al. 2012

The Anatomical Record

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Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit.

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Section: Postnatal Morphology Of Olfactory Mucosa In Rabbitsmentioning

confidence: 99%

Morphofunctional Adaptations of the Olfactory Mucosa in Postnatally Developing Rabbits

Kavoi

Makanya

Plendl

et al. 2012

The Anatomical Record

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“…Previous ultrastructural experiments have suggested that the distal cilia are the main site of olfactory signal transduction, containing the molecular components of the cyclic nucleotide cascade (Menco et al, 1992;Menco, 1994). We therefore examined whether the fluorescence increase resulting from CNG channel activation showed a heterogeneous distribution in individual cilia, displaying higher intensity at distal cilia as compared with more proximal regions (Fig.…”

Section: Are There Domains Of Higher Fluorescence In Various Parts Ofmentioning

confidence: 99%

Calcium Entry through Cyclic Nucleotide-Gated Channels in Individual Cilia of Olfactory Receptor Cells: Spatiotemporal Dynamics

et al. 1997

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Transient elevations of intracellular Ca 2ϩ play an important role in regulating the sensitivity of olfactory transduction, but such elevations have not been demonstrated in the olfactory cilia, which are the site of primary odor transduction. To begin to understand Ca 2ϩ signaling in olfactory cilia, we used highresolution imaging techniques to study the Ca 2ϩ transients that occur in salamander olfactory receptor neurons (ORNs) as a result of cyclic nucleotide-gated (CNG) channel activation. To visualize ciliary Ca 2ϩ signals, we loaded ORNs with the Ca 2ϩ indicator dye Fluo-3 AM and measured fluorescence with a laser scanning confocal microscope. Application of the phosphodiesterase inhibitor IBMX increased fluorescence in the cilia and other neuronal compartments; the ciliary signal occurred first and was more transient. This signal could be abolished by lowering external Ca 2ϩ or by applying LY83583, a potent blocker of CNG channels, indicating that Ca 2ϩ entry through CNG channels was the primary source of fluorescence increases. Direct activation of CNG channels with low levels of 8-Br-cGMP (1 M) led to tonic Ca 2ϩ signals that were restricted locally to the cilia and the dendritic knob. Elevated external K ϩ , which depolarizes cell membranes, increased fluorescence signals in the cell body and dendrite but failed to increase ciliary Ca 2ϩ fluorescence. The results demonstrate the existence and spatiotemporal properties of Ca 2ϩ transients in individual olfactory cilia and implicate CNG channels as a major pathway for Ca 2ϩ entry into ORN cilia during odor transduction.

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“…Because the ACIII is almost exclusively expressed in the cilia, cAMP produced in this compartment must diffuse to the knobs to activate the CNG channel. Alternatively, the components of the olfactory transduction machinery may be expressed at low levels in the knob (44,45), leaving open the option that locally produced cAMP activates the mislocalized CNGB1 Ϫ/Ϫ channel. Because the CNGB1 Ϫ/Ϫ channel shows much slower Ca 2ϩ -CaM-dependent inhibition, once activated, it would remain in the open state for a longer time period than the wild-type channel.…”

Section: Cngb1mentioning

confidence: 99%

Loss of CNGB1 Protein Leads to Olfactory Dysfunction and Subciliary Cyclic Nucleotide-gated Channel Trapping

Michalakis

Reisert

Geiger

et al. 2006

Journal of Biological Chemistry

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Olfactory receptor neurons (ORNs) employ a cyclic nucleotide-gated (CNG) channel to generate a receptor current in response to an odorant-induced rise in cAMP. This channel contains three types of subunits, the principal CNGA2 subunit and two modulatory subunits (CNGA4 and CNGB1b). Here, we have analyzed the functional relevance of CNGB1 for olfaction by gene targeting in mice. Electro-olfactogram responses of CNGB1-deficient (CNGB1 ؊/؊ ) mice displayed a reduced maximal amplitude and decelerated onset and recovery kinetics compared with wild-type mice. In a behavioral test, CNGB1؊/؊ mice exhibited a profoundly decreased olfactory performance. Electrophysiological recordings revealed that ORNs of CNGB1 ؊/؊ mice weakly expressed a CNG current with decreased cAMP sensitivity, very rapid flicker-gating behavior and no fast modulation by Ca 2؉ -calmodulin. Co-immunoprecipitation confirmed the presence of a CNGA2/CNGA4 channel in the olfactory epithelium of CNGB1 ؊/؊ mice. This CNGA2/CNGA4 channel was targeted to the plasma membrane of olfactory knobs, but failed to be trafficked into olfactory cilia. Interestingly, we observed a similar trafficking defect in mice deficient for the CNGA4 subunit. In conclusion, these results demonstrate that CNGB1 has a dual function in vivo. First, it endows the olfactory CNG channel with a variety of biophysical properties tailored to the specific requirements of olfactory transduction. Second, together with the CNGA4 subunit, CNGB1 is needed for ciliary targeting of the olfactory CNG channel. Cyclic nucleotide-gated (CNG)3 channels are molecular switches converting receptor-mediated increases in cytosolic concentrations of cAMP or cGMP into an influx of cations. The channels play a key role in visual and olfactory transductions. The CNG channel involved in olfaction is expressed at high density in the sensory cilia of olfactory receptor neurons (ORNs) where it is activated by an odorant-induced rise of cAMP. When open, the channel conducts mainly Ca 2ϩ and Na ϩ (1, 2). The subsequent rise in internal Ca 2ϩ

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Ultrastructural localization of olfactory transduction components: the G protein subunit Golfα and type III adenylyl cyclase

Cited by 112 publications

References 69 publications

Morphofunctional Adaptations of the Olfactory Mucosa in Postnatally Developing Rabbits

Morphofunctional Adaptations of the Olfactory Mucosa in Postnatally Developing Rabbits

Calcium Entry through Cyclic Nucleotide-Gated Channels in Individual Cilia of Olfactory Receptor Cells: Spatiotemporal Dynamics

Loss of CNGB1 Protein Leads to Olfactory Dysfunction and Subciliary Cyclic Nucleotide-gated Channel Trapping

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