Elementary Response of Olfactory Receptor Neurons to Odorants

Bhandawat, Vikas; Reisert, Johannes; Yau, King Wai

doi:10.1126/science.1109886

Cited by 140 publications

(141 citation statements)

References 23 publications

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“…Recent electrophysiological work has suggested that the termination of the activity of the receptor is simply caused by unbinding of the odorant molecule (Bhandawat et al, 2005). Our data now suggest that, at least during prolonged and/or intense stimulation of ORs, desensitization involves phosphorylation and recruitment of arrestins.…”

Section: Discussionsupporting

confidence: 55%

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Mashukova¹,

Spehr²,

Hatt³

et al. 2006

J. Neurosci.

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␤-arrestin2 with high affinity and are internalized via a clathrin-dependent mechanism. After prolonged odorant exposure, receptors are not targeted to lysosomal degradation but accumulate in recycling endosomes. Odorant-induced odorant receptor desensitization is promoted by cAMPdependent protein kinase A phosphorylation and is dependent on serine and threonine residues within the third intracellular loop of the receptor. Moreover, ␤-arrestin2 is redistributed into the dendritic knobs of mouse olfactory receptor neurons after treatment with a complex odorant mixture. Prolonged odorant exposure resulted in accumulation of ␤-arrestin2 in intracellular vesicles. Adaptation of olfactory receptor neurons to odorants can be abolished by the inhibition of clathrin-mediated endocytosis, showing the physiological relevance of the here described mechanism of odorant receptor desensitization. A better understanding of odorant receptor trafficking and additional insight into the molecular determinants underlying the interactions of odorant receptors with ␤-arrestin2 and other trafficking proteins will therefore be important to fully understand the mechanisms of adaptation and sensitization in the olfactory epithelium.

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Section: Discussionsupporting

confidence: 55%

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Mashukova¹,

Spehr²,

Hatt³

et al. 2006

J. Neurosci.

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“…7, green), the odorinduced synthesis of cAMP, operates with low efficiency (30,31). A few μM cAMP is, however, sufficient to activate the cAMP-gated transduction channels.…”

Section: Discussionmentioning

confidence: 99%

Molecular components of signal amplification in olfactory sensory cilia

Hengl

Kaneko

Dauner

et al. 2010

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

100

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The mammalian olfactory system detects an unlimited variety of odorants with a limited set of odorant receptors. To cope with the complexity of the odor world, each odorant receptor must detect many different odorants. The demand for low odor selectivity creates problems for the transduction process: the initial transduction step, the synthesis of the second messenger cAMP, operates with low efficiency, mainly because odorants bind only briefly to their receptors. Sensory cilia of olfactory receptor neurons have developed an unusual solution to this problem. They accumulate chloride ions at rest and discharge a chloride current upon odor detection. This chloride current amplifies the receptor potential and promotes electrical excitation. We have studied this amplification process by examining identity, subcellular localization, and regulation of its molecular components. We found that the Na + /K + /2Cl − cotransporter NKCC1 is expressed in the ciliary membrane, where it mediates chloride accumulation into the ciliary lumen. Gene silencing experiments revealed that the activity of this transporter depends on the kinases SPAK and OSR1, which are enriched in the cilia together with their own activating kinases, WNK1 and WNK4. A second Cl − transporter, the Cl − /HCO 3 − exchanger SLC4A1, is expressed in the cilia and may support Cl − accumulation. The calcium-dependent chloride channel TMEM16B (ANO2) provides a ciliary pathway for the excitatory chloride current. These findings describe a specific set of ciliary proteins involved in anion-based signal amplification. They provide a molecular concept for the unique strategy that allows olfactory sensory neurons to operate as efficient transducers of weak sensory stimuli.chloride | olfaction | sensory transduction | transport | kinase M ammalian olfactory receptor neurons (ORNs) present to the air a tuft of sensory cilia equipped with odorant receptors. Upon contact with odorants, these receptors actuate a transduction cascade that leads to firing of action potentials. This cascade has an unusual, two-stage organization (1). First, the activated odorant receptors induce a rise of the second messengers cAMP and Ca 2+ in the cilia, a process that involves cAMP-gated, Ca 2+ -permeable ion channels. In the second stage, inflowing Ca 2+ opens Cl − channels. By conducting a depolarizing Cl − efflux from the cilia, these channels amplify the receptor potential approximately 10-fold, thus helping to excite the neuron even when stimulation is weak. ORNs accumulate chloride through the Na + /K + /2Cl − cotransporter NKCC1 and maintain an elevated intracellular Cl − concentration (2, 3) to support amplification. Accordingly, gene ablation of NKCC1, as well as the pharmacologic suppression of Cl − accumulation or Cl − efflux, strongly inhibits the sensory response of ORNs (3-5). Although these observations provide a robust concept for signal amplification, several points are still unclear. These concern both the Cl − accumulation process and the excitatory Cl − currents. First, ...

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“…However, olfactory neurons are intermittently exposed to variable concentrations of an odorant as the animal moves through the medium and turbulent air-flows carry odorant molecules. Furthermore, signal amplification does not seem to take place at the level of olfactory neurons because of the low efficacy with which olfactory receptors translate odorant binding into biochemical (Takeuchi and Kurahashi, 2005) and electrical (Bhandawat et al, 2005) signals. The high number of olfactory neurons expressing a given olfactory receptor may compensate for this low efficacy.…”

Section: The Importance Of a Glomerular Amplifiermentioning

confidence: 99%

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

Jan¹,

Westbrook²

2007

J. Neurosci.

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Sensory systems often respond to rapid stimuli with high frequency and fidelity, as perhaps best exemplified in the auditory system. Fast synaptic responses are fundamental requirements to achieve this task. The importance of speed is less clear in the olfactory system. Moreover, olfactory bulb output mitral cells respond to a single stimulation of the sensory afferents with unusually long EPSPs, lasting several seconds. We examined the temporal characteristics, developmental regulation, and the mechanism generating these responses in mouse olfactory bulb slices. The slow EPSP appeared at postnatal days 10 -11 and was mediated by metabotropic glutamate receptor 1 (mGluR1) and NMDA receptors. mGluR1 contribution was unexpected because its activation usually requires strong, high-frequency stimulation of inputs. However, dendritic release of glutamate from the intraglomerular network caused spillover-mediated recurrent activation of metabotropic glutamate receptors. We suggest that persistent responses in mitral cells amplify the incoming sensory information and, along with asynchronous inputs, drive odor-evoked slow temporal activity in the bulb.

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Elementary Response of Olfactory Receptor Neurons to Odorants

Cited by 140 publications

References 23 publications

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Molecular components of signal amplification in olfactory sensory cilia

Disynaptic Amplification of Metabotropic Glutamate Receptor 1 Responses in the Olfactory Bulb

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