Differentially expressed transcripts from phenotypically identified olfactory sensory neurons

Yu, Tun-Tzu; McIntyre, Jeremy C.; Bose, Soma C.; Hardin, Debra L.; Owen, Michael C.; McClintock, Timothy S.

doi:10.1002/cne.20429

Cited by 86 publications

(91 citation statements)

References 76 publications

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“…Ano2 transcripts are highly expressed in the olfactory system (GNF Symatlas and Genepaint), specifically in OSNs (20). Using independent in situ hybridization probes, we confirmed that Ano2 mRNA localized specifically to OSNs within the OE and not to the sustentacular or basal stem cell layers (Fig.…”

Section: Ano2 Is Present In a Preparation Of Olfactory Cilial Membranessupporting

confidence: 65%

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ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification

Stephan

Shum²,

Hirsh³

et al. 2009

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

303

377

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For vertebrate olfactory signal transduction, a calcium-activated chloride conductance serves as a major amplification step. However, the molecular identity of the olfactory calcium-activated chloride channel (CaCC) is unknown. Here we report a proteomic screen for cilial membrane proteins of mouse olfactory sensory neurons (OSNs) that identified all the known olfactory transduction components as well as Anoctamin 2 (ANO2). Ano2 transcripts were expressed specifically in OSNs in the olfactory epithelium, and ANO2::EGFP fusion protein localized to the OSN cilia when expressed in vivo using an adenoviral vector. Patch-clamp analysis revealed that ANO2, when expressed in HEK-293 cells, forms a CaCC and exhibits channel properties closely resembling the native olfactory CaCC. Considering these findings together, we propose that ANO2 constitutes the olfactory calciumactivated chloride channel.Anoctamin ͉ cilia ͉ olfaction ͉ signal transduction ͉ TMEM16B

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Section: Ano2 Is Present In a Preparation Of Olfactory Cilial Membranessupporting

confidence: 65%

“…S6 and Table S3 ), ANO2 was the only ANO protein found in our proteomic screen. Additionally, no other Ano family member transcripts have been found to be OSN-specific (20). Bestrophin 2 (Best2) has been proposed as a candidate olfactory CaCC (29).…”

Section: Discussionmentioning

confidence: 99%

ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification

Stephan

Shum²,

Hirsh³

et al. 2009

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

303

377

View full text Add to dashboard Cite

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“…However, both SUS1 and nestin antibodies also label cells of Bowman's glands, which lie within the lamina propria of the OE, suggesting that Bowman's gland epithelial cells and SUS cells may share a common progenitor, as has been hypothesized previously [9,22]. Other reports also indicate that SUS cells and respiratory epithelium share some antigenic properties [25], suggesting that SUS cells may not be part of the OE neural lineage.…”

Section: Sustentacular Cell Originsmentioning

confidence: 73%

“…This selfrenewing, non-neuronal cell type expresses enzymes involved in metabolizing foreign compounds (cytochrome p450, glutathione-S-transferase mu 2, and carbonyl reductase 2; [25]), suggesting a role for SUS cells in detoxifying many of the noxious substances present in the air, to which the OE is exposed. SUS cells also phagocytose dead ORNs [26], and much like the glia of the brain, probably provide structural support to ORNs.…”

Section: Sustentacular Cell Originsmentioning

confidence: 99%

Identification and molecular regulation of neural stem cells in the olfactory epithelium

Beites

Kawauchi

Crocker

et al. 2005

Experimental Cell Research

238

234

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The sensory neurons that subserve olfaction, olfactory receptor neurons (ORNs), are regenerated throughout life, making the neuroepithelium in which they reside [the olfactory epithelium (OE)] an excellent model for studying how intrinsic and extrinsic factors regulate stem cell dynamics and neurogenesis during development and regeneration. Numerous studies indicate that transcription factors and signaling molecules together regulate generation of ORNs from stem and progenitor cells during development, and work on regenerative neurogenesis indicates that these same factors may operate at postnatal ages as well. This review describes our current knowledge of the identity of the OE neural stem cell; the different cell types that are thought to be the progeny (directly or indirectly) of this stem cell; and the factors that influence cell differentiation in the OE neuronal lineage. We review data suggesting that (1) the ORN lineage contains three distinct proliferating cell types-a stem cell and two populations of transit amplifying cells; (2) in established OE, these three cell types are present within the basal cell compartment of the epithelium; and (3) the stem cell that gives rise ultimately to ORNs may also generate two glial cell types of the primary olfactory pathway: sustentacular cells (SUS), which lie within OE proper; and olfactory ensheathing cells (OEC), which envelope the olfactory nerve. In addition, we describe factors that are both made by and found within the microenvironment of OE stem and progenitor cells, and which exert crucial growth regulatory effects on these cells. Thus, as with other regenerating tissues, the basis of regeneration in the OE appears be a population of stem cells, which resides within a microenvironment (niche) consisting of factors crucial for maintenance of its capacity for proliferation and differentiation. D

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“…The family of TMEM16 (alias: anoctamin) proteins have recently been shown to form Ca 2+ -activated Cl − channels (7,(21)(22)(23)(24). The mRNA of this protein was located in rodent ORNs (8,25), and TMEM16B is the only of the 10 TMEM16 isoforms present in the ciliary proteome (8,20). We detected the mRNA expression of TMEM16B in cDNA obtained from ORNs that were FACS purified.…”

Section: Nkcc1 Expressionmentioning

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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Differentially expressed transcripts from phenotypically identified olfactory sensory neurons

Cited by 86 publications

References 76 publications

ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification

ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification

Identification and molecular regulation of neural stem cells in the olfactory epithelium

Molecular components of signal amplification in olfactory sensory cilia

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