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PLoS One
2017 Sep 08;129:e0185329. doi: 10.1371/journal.pone.0185329.
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Mammalian odorant receptor tuning breadth persists across distinct odorant panels.
Kepchia D
,
Sherman B
,
Haddad R
,
Luetje CW
.
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The molecular receptive range (MRR) of a mammalian odorant receptor (OR) is the set of odorant structures that activate the OR, while the distribution of these odorant structures across odor space is the tuning breadth of the OR. Variation in tuning breadth is thought to be an important property of ORs, with the MRRs of these receptors varying from narrowly to broadly tuned. However, defining the tuning breadth of an OR is a technical challenge. For practical reasons, a screening panel that broadly covers odor space must be limited to sparse coverage of the many potential structures in that space. When screened with such a panel, ORs with different odorant specificities, but equal tuning breadths, might appear to have different tuning breadths due to chance. We hypothesized that ORs would maintain their tuning breadths across distinct odorant panels. We constructed a new screening panel that was broadly distributed across an estimated odor space and contained compounds distinct from previous panels. We used this new screening panel to test several murine ORs that were previously characterized as having different tuning breadths. ORs were expressed in Xenopus laevis oocytes and assayed by two-electrode voltage clamp electrophysiology. MOR256-17, an OR previously characterized as broadly tuned, responded to nine novel compounds from our new screening panel that were structurally diverse and broadly dispersed across an estimated odor space. MOR256-22, an OR previously characterized as narrowly tuned, responded to a single novel compound that was structurally similar to a previously known ligand for this receptor. MOR174-9, a well-characterized receptor with a narrowly tuned MRR, did not respond to any novel compounds in our new panel. These results support the idea that variation in tuning breadth among these three ORs is not an artifact of the screening protocol, but is an intrinsic property of the receptors.
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Fig 1. Distribution of our new odorant panel in an estimated odor space.Odor space was estimated using 1595 molecules (blue dots) in a multidimensional space based on 32 physiochemical descriptors and plotted using the first and second principal components. The 60 odorants in our screening panel are indicated with small red circles. One odorant (trans-cinnamaldehyde, green star) was included from our previous panel for reference. (A) The entire odor space is shown, including an extreme outlier (iodoform). The smallest hypersphere (indicated by the large red ellipse) that could encompass all odorants in our screening panel (including iodoform) had a radius of 43.0. (B) A close-up view of the region containing all of the molecules (excluding iodoform) is shown. The smallest hypersphere (indicated by the large red ellipse) that could encompass the odorants in our screening panel (excluding iodoform) had a radius of 15.5.
Fig 2. MOR256-17 remains broadly tuned, responding to diverse chemical structures.(A) Current recordings of oocytes expressing MOR256-17, Gαolf and CFTR. Odorants were screened in 6 mixtures, with each odorant present at 30 μM. Cyclodecanone (CYD) was screened individually. An application of 2-heptanone (2-HE) is included at the end of each trace for normalization. Representative traces are shown (n = 5–8). (B) Representative current recordings (n = 3–6) of the six odorant mixtures, as well as iodoform (IOD) and cyclodecanone (CYD), applied to sham (water) injected oocytes. Each odorant was present at 30 μM. (C) Representative current recordings of oocytes expressing MOR256-17, Gαolf and CFTR responding to individual odorants applied at 30 μM. Four of the nine novel odorants we identified as activators of MOR256-17 are shown: methyl hexanoate (MHX), bromobenzene (BRO), amyl methyl sulfide (AMS) and iodoform (IOD). Also shown is the previously identified MOR256-17 ligand, trans-cinnamaldehyde (TCN), that was included in Mixture 4. Several inactive compounds are also shown: isoamyl phenylacetate (IPA), α-hexyl cinnamaldehyde (HC), dimethyl succinate (DMS), isoborneol (IBN), and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyran (HBB). An application of 2-HE is included at the end of each trace for normalization. (D) Responses to nine newly identified odorant ligands were normalized to the response to 2-HE and are presented as mean ± SEM (n = 6–9). In addition to the compounds shown in panel C: 3-octanol (3-OL), toluene (TOL), 2-isobutyl-3-methoxypyrazine (IMP), isophorone (ISO) and piperonal (PIP).
Fig 3. MOR256-22 remains narrowly tuned, responding to structurally similar odorants.(A) Current recordings of oocytes expressing MOR256-22, Gαolf and CFTR. Odorants were screened in 6 mixtures, with each odorant present at 30 μM. Cyclodecanone (CYD) and iodoform (IOD) were screened individually. Responses were normalized to the trans-cinnamaldehyde (TCN) response. Representative traces are shown (n = 4–8). (B) Current recording of an oocyte expressing MOR256-22, Gαolf and CFTR responding to individual odorants. MOR256-22 only responded to the previously identified odorant ligand (trans-cinnamaldehyde) and α,α-dimethylbenzenepropanol (DBP), a structurally similar novel activator. A representative trace is shown (n = 9).
Fig 4. MOR174-9 does not respond to the new panel of odorants.Current recordings of oocytes expressing MOR174-9, Gαolf and CFTR. Odorants were screened in 6 mixtures, with each odorant present at 30 μM. Cyclodecanone (CYD) and iodoform (IOD) were screened individually. Responses were normalized to the eugenol (EUG) response. Representative traces are shown (n = 4–5).
Fig 5. The molecular receptive range remains broad for MOR256-17 and narrow for MO256-22.(A,B) Active odorant ligands for MOR256-17 (red circles) are plotted within an estimated odor space. (A) The smallest hypersphere (indicated by the large red ellipse) that could encompass all odorants that activated the receptor had a radius of 38.6. (B) If iodoform was excluded, the value was 8.1. (C,D) Active odorant ligands for MOR256-22 (red circles) are plotted within an estimated odor space. The smallest hypersphere (indicated by the large red ellipse) that could encompass all odorants that activated the receptor was 3.4. Panels A and C show the entire odor space, including an extreme outlier (iodoform). Panels B and D show a close-up view of the region containing all of the odorants (excluding iodoform). The green star indicates trans-cinnamaldehyde.
Abaffy,
Functional analysis of a mammalian odorant receptor subfamily.
2006, Pubmed,
Xenbase
Abaffy,
Functional analysis of a mammalian odorant receptor subfamily.
2006,
Pubmed
,
Xenbase
Araneda,
The molecular receptive range of an odorant receptor.
2000,
Pubmed
Bakalyar,
Identification of a specialized adenylyl cyclase that may mediate odorant detection.
1990,
Pubmed
Baud,
The mouse eugenol odorant receptor: structural and functional plasticity of a broadly tuned odorant binding pocket.
2011,
Pubmed
Bavan,
Discovery of novel ligands for mouse olfactory receptor MOR42-3 using an in silico screening approach and in vitro validation.
2014,
Pubmed
,
Xenbase
Bozza,
Odorant receptor expression defines functional units in the mouse olfactory system.
2002,
Pubmed
Dahoun,
Recombinant expression and functional characterization of mouse olfactory receptor mOR256-17 in mammalian cells.
2011,
Pubmed
Dunkel,
Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology.
2014,
Pubmed
Firestein,
The relation between stimulus and response in olfactory receptor cells of the tiger salamander.
1993,
Pubmed
Firestein,
How the olfactory system makes sense of scents.
2001,
Pubmed
Geithe,
The Broadly Tuned Odorant Receptor OR1A1 is Highly Selective for 3-Methyl-2,4-nonanedione, a Key Food Odorant in Aged Wines, Tea, and Other Foods.
2017,
Pubmed
Godfrey,
The mouse olfactory receptor gene family.
2004,
Pubmed
Grosmaitre,
SR1, a mouse odorant receptor with an unusually broad response profile.
2009,
Pubmed
Haddad,
A metric for odorant comparison.
2008,
Pubmed
Haddad,
Global features of neural activity in the olfactory system form a parallel code that predicts olfactory behavior and perception.
2010,
Pubmed
Jones,
Golf: an olfactory neuron specific-G protein involved in odorant signal transduction.
1989,
Pubmed
Kajiya,
Molecular bases of odor discrimination: Reconstitution of olfactory receptors that recognize overlapping sets of odorants.
2001,
Pubmed
Katada,
Structural basis for a broad but selective ligand spectrum of a mouse olfactory receptor: mapping the odorant-binding site.
2005,
Pubmed
Krautwurst,
Identification of ligands for olfactory receptors by functional expression of a receptor library.
1998,
Pubmed
Li,
A broadly tuned mouse odorant receptor that detects nitrotoluenes.
2012,
Pubmed
Li,
Receptive range analysis of a mouse odorant receptor subfamily.
2015,
Pubmed
,
Xenbase
Lowe,
Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells.
1993,
Pubmed
Ma,
High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening.
2002,
Pubmed
Malnic,
Combinatorial receptor codes for odors.
1999,
Pubmed
Mombaerts,
Visualizing an olfactory sensory map.
1996,
Pubmed
Mori,
The olfactory bulb: coding and processing of odor molecule information.
1999,
Pubmed
Nakamura,
A cyclic nucleotide-gated conductance in olfactory receptor cilia.
,
Pubmed
Nara,
A large-scale analysis of odor coding in the olfactory epithelium.
2011,
Pubmed
Noe,
OR2M3: A Highly Specific and Narrowly Tuned Human Odorant Receptor for the Sensitive Detection of Onion Key Food Odorant 3-Mercapto-2-methylpentan-1-ol.
2017,
Pubmed
Repicky,
Molecular receptive range variation among mouse odorant receptors for aliphatic carboxylic acids.
2009,
Pubmed
,
Xenbase
Saito,
Odor coding by a Mammalian receptor repertoire.
2009,
Pubmed
Saito,
RTP family members induce functional expression of mammalian odorant receptors.
2004,
Pubmed
Serizawa,
Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse.
2003,
Pubmed
Sicard,
Receptor cell responses to odorants: similarities and differences among odorants.
1984,
Pubmed
Tazir,
The extremely broad odorant response profile of mouse olfactory sensory neurons expressing the odorant receptor MOR256-17 includes trace amine-associated receptor ligands.
2016,
Pubmed
Trimmer,
Simplifying the Odor Landscape.
2017,
Pubmed
Uezono,
Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Young,
Different evolutionary processes shaped the mouse and human olfactory receptor gene families.
2002,
Pubmed
Yu,
Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism.
2015,
Pubmed
Zhang,
The olfactory receptor gene superfamily of the mouse.
2002,
Pubmed