Mammalian olfactory receptors

Fleischer, Joerg

doi:10.3389/neuro.03.009.2009

Cited by 104 publications

(81 citation statements)

References 155 publications

(213 reference statements)

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“…OR gene families have evolved independently many times (36). Even within the same species, odorant detection is mediated by several distinct gene families, e.g., trace amine-associated receptors and guanylyl cyclase type D receptors mediate odorant recognition in the cilia of mouse OSNs in addition to the canonical G proteincoupled ORs.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Maurya

Bohm

Alenius

2017

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

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The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients. The ciliary phenotype of Smo inhibition is haploinsufficient, cell autonomous, and correlates with the accumulation of OR-containing putative transport vesicles in the cytosol. The Smo-dependent OR transport route works in parallel with a low basal transport of vesicle containing both ORs and other olfactory transduction components. These findings both define a physiological function of Hedgehog signaling in olfaction and provide an important evolutionary link between olfaction and the requirement of a ciliary compartment for Hedgehog signaling.

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Section: Discussionmentioning

confidence: 99%

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Maurya

Bohm

Alenius

2017

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

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“…Moreover, MOE-specific expression was found in a large percentage (50%) of the v2r genes analyzed here. This pattern of expression is very different from the ectopic or broad expression of sporadic mammalian or and v1r genes (20,21) and diametrically opposite to the very rare cells occasionally seen for more modern v2r genes of subgroup A2 and A3 both in larval MOE [this study and results by Hagino-Yamagish et al (2)] and adult middle cavity (2), a subdivision of the MOE arising during metamorphosis (22). In fact, the restriction of the more ancestral v2r genes to the MOE is even stricter than that of the more modern v2r genes to the VNO, because we did not find a single exception in over 400 counted cells.…”

Section: Discussionmentioning

confidence: 99%

Ancestral amphibian v2r s are expressed in the main olfactory epithelium

Syed

Sansone

Nadler

et al. 2013

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

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Mammalian olfactory receptor families are segregated into different olfactory organs, with type 2 vomeronasal receptor (v2r) genes expressed in a basal layer of the vomeronasal epithelium. In contrast, teleost fish v2r genes are intermingled with all other olfactory receptor genes in a single sensory surface. We report here that, strikingly different from both lineages, the v2r gene family of the amphibian Xenopus laevis is expressed in the main olfactory as well as the vomeronasal epithelium. Interestingly, late diverging v2r genes are expressed exclusively in the vomeronasal epithelium, whereas "ancestral" v2r genes, including the single member of v2r family C, are restricted to the main olfactory epithelium. Moreover, within the main olfactory epithelium, v2r genes are expressed in a basal zone, partially overlapping, but clearly distinct from an apical zone of olfactory marker protein and odorant receptor-expressing cells. These zones are also apparent in the spatial distribution of odor responses, enabling a tentative assignment of odor responses to olfactory receptor gene families. Responses to alcohols, aldehydes, and ketones show an apical localization, consistent with being mediated by odorant receptors, whereas amino acid responses overlap extensively with the basal v2r-expressing zone. The unique bimodal v2r expression pattern in main and accessory olfactory system of amphibians presents an excellent opportunity to study the transition of v2r gene expression during evolution of higher vertebrates. To what extent such differences influence the coding and discrimination abilities of the respective olfactory systems is unclear, and the evolutionary path toward such segregation is unknown.

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“…Because of each OSN expressing only one type of the roughly 1,000 functional ORs present in mice and rat (3,20,21), individual species of these seven transmembrane (TM) domain receptors are of very low abundance and are thus difficult to detect. Moreover, the hydrophobic nature of integral membrane proteins still represents a major challenge in current proteomics research (22).…”

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confidence: 99%

The Membrane Proteome of Sensory Cilia to the Depth of Olfactory Receptors

Kuhlmann

Tschapek

Wiese

et al. 2014

Molecular & Cellular Proteomics

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In the nasal cavity, the nonmotile cilium of olfactory sensory neurons (OSNs) constitutes the chemosensory interface between the ambient environment and the brain. The unique sensory organelle facilitates odor detection for which it includes all necessary components of initial and downstream olfactory signal transduction. In addition to its function in olfaction, a more universal role in modulating different signaling pathways is implicated, for example, in neurogenesis, apoptosis, and neural regeneration. To further extend our knowledge about this multifunctional signaling organelle, it is of high importance to establish a most detailed proteome map of the ciliary membrane compartment down to the level of transmembrane receptors. We detached cilia from mouse olfactory epithelia via Ca 2؉ /K ؉ shock followed by the enrichment of ciliary membrane proteins at alkaline pH, and we identified a total of 4,403 proteins by gel-based and gel-free methods in conjunction with high resolution LC/MS. This study is the first to report the detection of 62 native olfactory receptor proteins and to provide evidence for their heterogeneous expression at the protein level. Quantitative data evaluation revealed four ciliary membrane-associated candidate proteins (the annexins ANXA1, ANXA2, ANXA5, and S100A5) with a suggested function in the regulation of olfactory signal transduction, and their presence in ciliary structures was confirmed by immunohistochemistry. Moreover, we corroborated the ciliary localization of the potassium-dependent Na ؉ /Ca 2؉ exchanger (NCKX) 4 and the plasma membrane Ca 2؉ -ATPase 1 (PMCA1) involved in olfactory signal termination, and we detected for the first time NCKX2 in olfactory cilia. Through comparison with transcriptome data specific for mature, ciliated OSNs, we finally delineated the membrane ciliome of OSNs. The membrane proteome of olfactory cilia established here is the most complete today, thus allowing us to pave new avenues for the study of diverse molecular functions and signaling pathways in and out of olfactory cilia and thus to advance our understanding of the biology of sensory organelles in general. Molecular & Cellular Proteomics 13:

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Mammalian olfactory receptors

Cited by 104 publications

References 155 publications

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Ancestral amphibian v2r s are expressed in the main olfactory epithelium

The Membrane Proteome of Sensory Cilia to the Depth of Olfactory Receptors

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