A Sensor for Low Environmental Oxygen in the Mouse Main Olfactory Epithelium

Bleymehl, Katherin; Pérez-Gómez, Anabel; Omura, Masayo; Moreno-Pérez, Ana; Macías, David; Bai, Zhaodai; Johnson, Randall S.; Leinders‐Zufall, Trese; Zufall, Frank; Mombaerts, Peter

doi:10.1016/j.neuron.2016.11.001

Cited by 47 publications

(68 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27d However, it was shown that the human musk-sensitive receptor OR5AN1, expressed in HEK293T cells derived from human embryonic kidney, and identified through screening of 330 similarly expressed human ORs as the sole bona fide receptor for cyclopentadecanone, fails to distinguish a series of deuterated and nondeuterated isotopologues of cyclopentadecanone and other musk odorants. Furthermore, pairs of deuterated and nondeuterated acetophenone, benzaldehyde, and several other deuterated and nondeuterated odorants, and pairs of 13 C and normal isotopologues of both acetophenone and benzaldehyde failed to show differences when tested against their respective, responsive ORs. 30 In addition, contrary to the claim that a musk receptor “detects vibrations in the 1380- to 1550-cm -1 range” where musks are said to have intense bands, 27d it was found that fully deuterated muscone, which strongly activates OR5AN1 equally as well as the undeuterated muscone, is devoid of 1380- to 1550-cm -1 absorption.…”

Section: Theories Of Olfactionmentioning

confidence: 95%

“…7a Non-GPCR chemosensors and oxygen chemosensors are also known. 13b,c In insect olfaction, not considered here, ORs are mainly located on the antennae and have significantly different structures than their vertebrate counterparts.…”

Section: Introduction: Odorants and The Olfactory Systemmentioning

confidence: 99%

“…12 The VNO, thought to be nonfunctional in adult humans, will not be considered here. 13a In addition to expressing ORs, OSNs also express two other types of olfactory receptors known as trace amine-associated receptors (TAARs), which respond to volatile amines at nanomolar ranges, and receptors that signal via guanylyl cyclase, which respond to both carbon dioxide and carbon disulfide, the latter at submicromolar levels. 7a Non-GPCR chemosensors and oxygen chemosensors are also known.…”

Section: Introduction: Odorants and The Olfactory Systemmentioning

confidence: 99%

See 2 more Smart Citations

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

et al. 2017

View full text Add to dashboard Cite

While suggestions concerning the possible role of metals in olfaction and taste date back 50 years, only recently has it been possible to confirm these proposals with experiments involving individual olfactory receptors (ORs). A detailed discussion of recent experimental results demonstrating the key role of metals in enhancing the response of human and other vertebrate ORs to specific odorants is presented against the backdrop of our knowledge of how the sense of smell functions both at the molecular and whole animal levels. This review emphasizes the role of metals in the detection of low molecular weight thiols, sulfides, and other organosulfur compounds, including those found in strong-smelling animal excretions and plant volatiles, and those used in gas odorization. Alternative theories of olfaction are described, with evidence favoring the modified “shape” theory. The use of quantum mechanical/molecular modeling (QM/MM), site-directed mutagenesis and saturation-transfer-difference (STD) NMR is discussed, providing support for biological studies of mouse and human receptors, MOR244-3 and OR OR2T11, respectively. Copper is bound at the active site of MOR244-3 by cysteine and histidine, while cysteine, histidine and methionine are involved with OR2T11. The binding pockets of these two receptors are found in different locations in the three-dimensional seven transmembrane models. Another recently deorphaned human olfactory receptor, OR2M3, highly selective for a thiol from onions, and a broadly-tuned thiol receptor, OR1A1, are also discussed. Other topics covered include the effects of nanoparticles and heavy metal toxicants on vertebrate and fish ORs, intranasal zinc products and the loss of smell (anosmia).

show abstract

Section: Theories Of Olfactionmentioning

confidence: 95%

Section: Introduction: Odorants and The Olfactory Systemmentioning

confidence: 99%

Section: Introduction: Odorants and The Olfactory Systemmentioning

confidence: 99%

See 1 more Smart Citation

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Physiological and biochemical studies of olfaction to date offer strong evidence that the majority of mammalian OR signalings are associated with G-protein dependent pathway [7]. Thus, except for a few cases [8,9,10], their activation mechanism is mostly related to that of G-protein coupled receptors (GPCRs) [11,12,13]. Upon binding odorants, a set of ORs adopt their structures into active forms and catalyze G-proteins to initiate downstream signal cascades.…”

Section: Introductionmentioning

confidence: 99%

Implications for human odor sensing revealed from the statistics of the odorant-receptor interactions

Bak

Jang

Hyeon

2018

Preprint

View full text Add to dashboard Cite

Binding of odorants to olfactory receptors (ORs) elicits downstream chemical and neural signals, which are further processed to odor perception in the brain. Recently, Mainland et al. [Sci. data, (2015) 2:sdata20152] have measured 500 pairs of odorant-OR interaction by a high-throughput screening assay method, opening a new avenue to understanding the principles of human odor coding. Here, using a recently developed minimal model for OR activation kinetics [J. Phys. Chem. B (2017) 121, 1304-1311], we characterize the statistics of OR activation by odorants in terms of three empirical parameters: the half-maximum effective concentration EC 50 , the efficacy, and the basal activity. While the data size of odorants is still limited, the statistics offer meaningful information on the breadth and optimality of the tuning of human ORs to odorants, and allow us to relate the three parameters with the microscopic rate constants and binding affinities that define the OR activation kinetics. Despite the stochastic nature of the response expected at individual OR-odorant level, we assess that the confluence of signals in a neuron released from the multitude of ORs is effectively free of noise and deterministic with respect to changes in odorant concentration. Thus, setting a threshold to the fraction of activated OR copy number for neural spiking binarizes the electrophysiological signal of olfactory sensory neuron, thereby making an information theoretic approach a viable tool in studying the principles of odor perception. IntroductionOlfaction, ubiquitous among all animals, is a key sensory process that is used to detect a vast number of chemicals in the external world [1,2]. From the perspective of molecular recognition, the physicochemical principle germane to the early layer of olfactory process is not significantly different from that of unicellular organisms' chemotactic response [3,4,5]. Similarly, olfactory signals are initiated upon the recognition of odorants by the receptors that are expressed in the nasal epithelium [6].Physiological and biochemical studies of olfaction to date offer strong evidence that the majority of mammalian OR signalings are associated with G-protein dependent pathway [7]. Thus, except for a few cases [8,9,10], their activation mechanism is mostly related to that of G-protein coupled receptors (GPCRs) [11,12,13]. Upon binding odorants, a set of ORs adopt their structures into active forms and catalyze G-proteins to initiate downstream signal cascades. Although the original input signal is modified passing through multiple layers of neural circuits [14,15], elucidating the information encoded to the pool of ORs is a key component for understanding the principles of odor sensing. In particular, the receptor code, or the responses of a repertoire of ORs encoding the chemical features of odorant(s), constitutes the first layer of dataset to be mapped by the olfactory process.Unlike the conventional GPCRs that are deemed 'fine-tuned' to endogenous agonists such as hormones and neurotransmitt...

show abstract

“…Two subpopulations of OSNs within the MOE also rely on cGMP signaling. One, a subset of OSNs that express the ion channel Trpc2, also contains the soluble guanylyl cyclase Gucy1b2 and the phosphodiesterase Pde6d, and uses cGMP signaling to respond to decreases in environmental O2 (Omura and Mombaerts, 2015;Bleymehl et al, 2016). The second expresses the receptor guanylyl cyclase GC-D (hence their typical designation as GC-D+ OSNs), Cnga3 and Pde2a (Fulle et al, 1995;Juilfs et al, 1997;Meyer et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion

Huang

Zimmerman

Munger

2018

Preprint

View full text Add to dashboard Cite

The main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascadeguanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) -project to distinct groups of "necklace" glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine-and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca 2+ /calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.

show abstract

A Sensor for Low Environmental Oxygen in the Mouse Main Olfactory Epithelium

Cited by 47 publications

References 29 publications

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

Implications for human odor sensing revealed from the statistics of the odorant-receptor interactions

Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion

Contact Info

Product

Resources

About