Distribution, Amplification, and Summation of Cyclic Nucleotide Sensitivities within Single Olfactory Sensory Cilia

Takeuchi, Hiroko; Kurahashi, Takashi

doi:10.1523/jneurosci.3531-07.2008

Cited by 31 publications

(54 citation statements)

References 54 publications

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“…3, 4), which has also been described by Duchamp-Viret et al (2000) for ORNs in rat and adult frog. The classical view is that odorant detection thresholds are determined by the affinity and expression level of olfactory receptors (Malnic et al, 1999;Kajiya et al, 2001;Saito et al, 2009), olfactory receptor dimerization (Neuhaus et al, 2004), as well as amplification and adaptation in the transduction cascade (Takeuchi and Kurahashi, 2008). We now show the significant contribution of the endocannabinoid 2-AG to the control of odorant thresholds.…”

Section: Discussionsupporting

confidence: 54%

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

Breunig¹,

Manzini²,

Piscitelli³

et al. 2010

Journal of Neuroscience

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Cannabinoids modulate the activity of many neuronal cells, among them sensory neurons in the olfactory epithelium. Here we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) is synthesized in both olfactory receptor neurons and glia-like sustentacular cells in larval Xenopus laevis. Its production in the latter depends on the hunger state of the animal. The essential effect of 2-AG in olfactory receptor neurons is the control of odorant detection thresholds via cannabinoid CB 1 receptor activation. Hunger renders olfactory neurons more sensitive. Endocannabinoid modulation in the nose may therefore substantially influence food-seeking behavior.

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Section: Discussionsupporting

confidence: 54%

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

Breunig¹,

Manzini²,

Piscitelli³

et al. 2010

Journal of Neuroscience

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“…1B). As no excitatory current was observed in response to TCA puffing alone, it is unlikely that the reduction in cAMP-induced response was caused by adaptation of the olfactory transduction mechanism (11)(12)(13)(14). Attenuation by 10 nM TCA was observed in all tested cells (N = 19; 1-μm diameter of puff pipette opening), consistent with suppression of a channel conductance (15) rather than inhibition via olfactory receptors (16).…”

Section: Resultsmentioning

confidence: 68%

2,4,6-Trichloroanisole is a potent suppressor of olfactory signal transduction

Takeuchi

Kato

Kurahashi

2013

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

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We investigated the sensitivity of single olfactory receptor cells to 2,4,6-trichloroanisole (TCA), a compound known for causing cork taint in wines. Such off-flavors have been thought to originate from unpleasant odor qualities evoked by contaminants. However, we here show that TCA attenuates olfactory transduction by suppressing cyclic nucleotide-gated channels, without evoking odorant responses. Surprisingly, suppression was observed even at extremely low (i.e., attomolar) TCA concentrations. The high sensitivity to TCA was associated with temporal integration of the suppression effect. We confirmed that potent suppression by TCA and similar compounds was correlated with their lipophilicity, as quantified by the partition coefficient at octanol/water boundary (pH 7.4), suggesting that channel suppression is mediated by a partitioning of TCA into the lipid bilayer of plasma membranes. The rank order of suppression matched human recognition of offflavors: TCA equivalent to 2,4,6-tribromoanisole, which is much greater than 2,4,6-trichlorophenol. Furthermore, TCA was detected in a wide variety of foods and beverages surveyed for odor losses. Our findings demonstrate a potential molecular mechanism for the reduction of flavor.olfactory masking | ion channel | patch-clamp T hroughout culinary history, consumers have been disturbed by naturally generated off-flavor substances that can greatly reduce the palatability of foods and beverages. Because off-flavors appear at very low concentrations of contaminants, chemical identification of responsible compounds has been limited. One of the most potent off-flavor compounds identified to date is 2,4,6-trichloroanisole (TCA), known specifically for inducing a cork taint in wines (1). In general, off-flavor compounds have been thought to induce unpleasant exogenous smells (2-9), and would therefore be expected to excite specific olfactory receptors (10) transducing malodors. However, we found that TCA did not generate excitatory responses in single olfactory receptor cells (ORCs), but potently suppressed cyclic nucleotide-gated (CNG) channels in these cells. Because CNG channels play a key role in olfactory transduction, suppression of these channels suggests a reduction of endogenous odors, rather than an addition of exogenous odors. Surprisingly, TCA exerted a much more potent suppressive effect on CNG channels (100-1,000-fold) than other known olfactory masking agents that have been widely used in perfumery. It was also more potent than a well-known CNG channel blocker, L-cis-diltiazem. We could account for such high suppressive potency in terms of temporal integration and slow recovery from suppression by TCA. The order of potency of CNG suppression by TCA analogues or precursors was identical to that of the human detection of the corresponding off-flavors, i.e., TCA equivalent to 2,4,6-tribromoanisole(TBA), which is much greater than 2,4,6-trichlorophenol (TCP; precursor of TCA), suggesting that cork taint is related to TCA suppression of CNG channels. We further confi...

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“…In vertebrate olfactory cilia, both CNG channels and Ca 2+ -gated chloride channels required for signal amplification are suggested to be clustered at the proximal end of the distal ciliary segment (Badamdorj et al, 2008;Flannery et al, 2006;Matsuzaki et al, 1999), although there might be organism-specific differences (Lowe and Gold, 1991;Takeuchi and Kurahashi, 2008). In Drosophila mechanosensory organs, a TRPN channel required for primary mechanotransduction is localized to the distal ciliary region, whereas TRPV channels that regulate signal amplification are instead localized to a proximal zone (Cheng et al, 2010;Lee et al, 2010;Liang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

Wojtyniak

Brear

O'Halloran

et al. 2013

Journal of Cell Science

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SummaryPrimary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis-and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein-and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell-and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions.

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Distribution, Amplification, and Summation of Cyclic Nucleotide Sensitivities within Single Olfactory Sensory Cilia

Cited by 31 publications

References 54 publications

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

The Endocannabinoid 2-Arachidonoyl-Glycerol Controls Odor Sensitivity in Larvae of Xenopus laevis

2,4,6-Trichloroanisole is a potent suppressor of olfactory signal transduction

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

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