Synchronous Evolution of an Odor Biosynthesis Pathway and Behavioral Response

Li, Qian; Korzan, Wayne J.; Ferrero, David M.; Chang, Rui B.; Roy, Dheeraj S.; Buchi, Mélanie; Lemon, Jamie K.; Kaur, Angeldeep W.; Stowers, Lisa; Fendt, Markus; Liberles, Stephen D.

doi:10.1016/j.cub.2012.10.047

Cited by 158 publications

(203 citation statements)

References 40 publications

(60 reference statements)

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“…Indeed, amines are an odor group that is chemically suited both to aquatic and airborne detection. Interestingly, trimethylamine, a TAAR5 agonist, is an aversive odor to humans and rats (20,33) but attractive to mice (20). This finding is reminiscent of cadaverine, which is attractive to goldfish (2) but aversive to zebrafish (present results).…”

Section: Discussionsupporting

confidence: 63%

“…We reasoned that a zebrafish TAAR could mediate the cadaverine avoidance behavior because several rodent TAARs detect biogenic amines, including some highly aversive odors (16,(18)(19)(20). As a result of numerous gene-duplication events, the zebrafish TAAR family is large, with 112 receptors encoded by the zebrafish genome (17).…”

Section: Cadaverine and Other Diamines Activate Sparse Olfactory Sensorymentioning

confidence: 99%

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High-affinity olfactory receptor for the death-associated odor cadaverine

Hussain

Saraiva

Ferrero

et al. 2013

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

161

234

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Carrion smell is strongly repugnant to humans and triggers distinct innate behaviors in many other species. This smell is mainly carried by two small aliphatic diamines, putrescine and cadaverine, which are generated by bacterial decarboxylation of the basic amino acids ornithine and lysine. Depending on the species, these diamines may also serve as feeding attractants, oviposition attractants, or social cues. Behavioral responses to diamines have not been investigated in zebrafish, a powerful model system for studying vertebrate olfaction. Furthermore, olfactory receptors that detect cadaverine and putrescine have not been identified in any species so far. Here, we show robust olfactory-mediated avoidance behavior of zebrafish to cadaverine and related diamines, and concomitant activation of sparse olfactory sensory neurons by these diamines. The large majority of neurons activated by low concentrations of cadaverine expresses a particular olfactory receptor, trace amineassociated receptor 13c (TAAR13c). Structure-activity analysis indicates TAAR13c to be a general diamine sensor, with pronounced selectivity for odd chains of medium length. This receptor can also be activated by decaying fish extracts, a physiologically relevant source of diamines. The identification of a sensitive zebrafish olfactory receptor for these diamines provides a molecular basis for studying neural circuits connecting sensation, perception, and innate behavior.Danio rerio | aversion | heterologous expression | polyamines C adaverine, putrescine, and other biogenic diamines are strongly repulsive odors to humans, for whom these odors presumably signal bacterial contamination. It may be expected that animal species feeding on carcasses attribute a more positive valence to diamines, and indeed both putrescine and cadaverine have been reported to be feeding attractants for rats (1) as well as goldfish (2). Similarly, insects depositing their eggs in carcasses or other proteineacous materials are attracted by these diamines (3). Beyond signaling danger or food, putrescine and cadaverine also serve as social cues in several vertebrate species, both for marking of territories-for example, in feline species (4)-and for burial of conspecifics (5).Very little is known about the molecular and cellular basis of cadaverine-driven behaviors. Cadaverine and putrescine evoke electrophysiological responses in the olfactory epithelium of two fish species (2, 6) and cadaverine-responsive olfactory sensory neurons and glomeruli have been identified in the mouse (7,8). However, chemosensory receptors that detect cadaverine or related diamines are unknown in any species, and could provide valuable tools to study how the olfactory system mediates innate aversion or attraction.Here, we show that cadaverine is a major product of zebrafish tissue decay, activates a zebrafish olfactory receptor (trace amineassociated receptor 13c, TAAR13c) with high affinity, and elicits a strong, low-threshold, and olfactory-mediated avoidance response in zebrafish. In vivo me...

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Section: Discussionsupporting

confidence: 63%

Section: Cadaverine and Other Diamines Activate Sparse Olfactory Sensorymentioning

confidence: 99%

High-affinity olfactory receptor for the death-associated odor cadaverine

Hussain

Saraiva

Ferrero

et al. 2013

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

161

234

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“…Although a receptor for TMAO has not yet been identified, its physiological precursor TMA has been described as activating a GPCR, TAAR5 25, 26. TAAR5 is thought to have evolved as a highly conserved olfactory receptor, enabling the detection of the pungent “fishy odor” of TMA 26, 27. Genetic ablation of TAAR5 in mice removes an attraction to TMA odor 27.…”

Section: Discussionmentioning

confidence: 99%

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB

Seldin

Meng

et al. 2016

JAHA

617

507

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BackgroundThe choline‐derived metabolite trimethylamine N‐oxide (TMAO) has been demonstrated to contribute to atherosclerosis and is associated with coronary artery disease risk.Methods and ResultsWe explored the impact of TMAO on endothelial and smooth muscle cell function in vivo, focusing on disease‐relevant outcomes for atherogenesis. Initially, we observed that aortas of LDLR −/− mice fed a choline diet showed elevated inflammatory gene expression compared with controls. Acute TMAO injection at physiological levels was sufficient to induce the same inflammatory markers and activate the well‐known mitogen‐activated protein kinase, extracellular signal–related kinase, and nuclear factor‐κB signaling cascade. These observations were recapitulated in primary human aortic endothelial cells and vascular smooth muscle cells. We also found that TMAO promotes recruitment of activated leukocytes to endothelial cells. Through pharmacological inhibition, we further showed that activation of nuclear factor‐κB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes.ConclusionsOur results suggest a likely contributory mechanism for TMAO‐dependent enhancement in atherosclerosis and cardiovascular risks.

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“…Like ORs, TAARs are evolutionarily conserved in vertebrates, suggesting that they may serve a distinct function. Ligands found thus far for TAARs are volatile amines, including several in mouse or predator urine (5,14,15). Ligands for a few mouse, fish, and human TAARs elicit aversive or attractive behaviors in their respective species, hinting at a conserved ability of TAARs to stimulate innate responses of potentially adaptive significance (5,6,14,16,17).…”

mentioning

confidence: 99%

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

Yoon

Ragoczy

et al. 2015

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

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The olfactory system translates a vast array of volatile chemicals into diverse odor perceptions and innate behaviors. Odor detection in the mouse nose is mediated by 1,000 different odorant receptors (ORs) and 14 trace amine-associated receptors (TAARs). ORs are used in a combinatorial manner to encode the unique identities of myriad odorants. However, some TAARs appear to be linked to innate responses, raising questions about regulatory mechanisms that might segregate OR and TAAR expression in appropriate subsets of olfactory sensory neurons (OSNs). Here, we report that OSNs that express TAARs comprise at least two subsets that are biased to express TAARs rather than ORs. The two subsets are further biased in Taar gene choice and their distribution within the sensory epithelium, with each subset preferentially expressing a subgroup of Taar genes within a particular spatial domain in the epithelium. Our studies reveal one mechanism that may regulate the segregation of Olfr (OR) and Taar expression in different OSNs: the sequestration of Olfr and Taar genes in different nuclear compartments. Although most Olfr genes colocalize near large central heterochromatin aggregates in the OSN nucleus, Taar genes are located primarily at the nuclear periphery, coincident with a thin rim of heterochromatin. Taar-expressing OSNs show a shift of one Taar allele away from the nuclear periphery. Furthermore, examination of hemizygous mice with a single Taar allele suggests that the activation of a Taar gene is accompanied by an escape from the peripheral repressive heterochromatin environment to a more permissive interior chromatin environment. olfactory receptor genes | Taar genes | nuclear organization

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Synchronous Evolution of an Odor Biosynthesis Pathway and Behavioral Response

Cited by 158 publications

References 40 publications

High-affinity olfactory receptor for the death-associated odor cadaverine

High-affinity olfactory receptor for the death-associated odor cadaverine

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB

Olfactory receptor genes expressed in distinct lineages are sequestered in different nuclear compartments

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