Olfaction odorant receptors

Olfaction, once thought to be a primitive sense, is now recognized as an elaborate sensory system that deploys a large family of odorant receptors to analyse the chemical environment. Interactions between these receptors and their diverse natural binding molecules (ligands) translate the world of odors into a neural code. Humans have about 350 odorant receptors. Rodents have more than a thousand. 

In vertebrates the neurons for olfaction are located in the nose mucosa and consist of short neurons with a peripheral ending endowed with odorant receptors for a large number of molecules in the environment. Each receptor neuron only contains one odorant receptor and is connected directly with the olfactory lobe of the brain. The vertebrate olfactory system must cope with a staggering developmental problem how to connect millions of olfactory neurons expressing different odorant receptors to appropriate targets in the brain. 

Here is a bit of a complication there is a lot of individual variation in the sense of human olfaction. Not everything smells the same to everyone. This holds both for the intensity of the perceived smeU as well as for its quality pleasant, floral, skunky, sweaty, or no odor at all. Andreas Keller has recently demonstrated that some significant part of this individual variation in the sense of smell derives from genetic variation in human odorant genes. Specifically, two single nucleotide polymorphisms (SNPs), leading to two amino acid substitutions in an odorant receptor, have dramatic affects on the perception of the odor of androstenone, a steroid derived from testosterone. 

These are exciting times in the field of chemosensory reception in general and olfaction in particular. In the decade since the landmark identification of a novel class of candidate odorant receptors (ORs) in rats (Buck and Axel, 1991), we have seen an explosion of similar studies involving other vertebrate as well as several insect species. In addition to an ever-increasing wealth of behavioral and physiological studies, insect systems provide arguably the most robust experimental system for the study of olfaction as well as a profound demonstration of the universal conservation of olfactory signal transduction mechanisms. 

Nef S., Allaman I., Fiumelli H., De Castro E. and Nef P. (1996) Olfaction in birds differential embryonic expression of nine putative odorant receptor genes in the avian olfactory system. Mech. Dev. 55, 65-77. 

Most olfaction models in the literature are far too simplistic and too mechanical in nature, and none of them have succeeded in accounting for all of the observations about olfaction. As described, recent advances in our understanding have confirmed that odor perception, as predicted by Polak (19), starts with a combinatorial mechanism at the receptor level (1) and involves pattern recognition in the higher brain (4). No single odorant-receptor interaction will be the sole determinant of odor percept, and even knowledge of the pattern elicited at the olfactory bulb is insufficient to enable prediction of the cortical image of odor. Therefore, structure/odor models are and, for the foreseeable future, will remain statistical tools rather than mechanistic indicators. 

Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB (2004) Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43 703-714... 

Ngai J, Alioto TS (2007) Genomics of odor receptors in zebrafish. In Firestein S, Beauchamp GK (eds) The senses a comprehensive reference, vol. 4. Olfaction and taste. Academic, Oxford,... 

Ha TS, Smith DP (2006) A pheromone receptor mediates 11-cis-vaccenyl acetate-induced responses in Drosophila. J Neurosci 26 8727-8733 Hallem EA et al (2004a) Olfaction mosquito receptor for human-sweat odorant. Nature 427 212-213... 

Kwon JY, Dahanukar A, Weiss LA, Carlson JR (2007) The molecular basis of C02 reception in Drosophila. Proc Natl Acad Sci USA 104 3574-3578 Laissue PP, Reiter C, Hiesinger PR, Halter S, Fischbach KF, Stocker RF (1999) Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster. J Comp Neurol 405 543-552 Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB (2004) Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43 703-714 Lacaille F, Hiroi M, Twele R, Inoshita T, Umemoto D, Maniere G, Marion-Poll F, Ozaki M, Francke W, Everaerts C, Tanimura T, Ferveur J-F (2007) A inhibitory sex pheromone tastes bitter for males. PLoS ONE 2 e661 Laurent G (1996) Odor images and tunes. Neuron 16 473-476... 

Figure 13.15 An alternative pictorial representation of the combinatorial mechanism of olfaction. Odorant 1 can trigger receptor A odorant 2 can trigger receptor B odorant 3 can trigger receptor C odorant 4 can trigger receptors A and C odorant 5 can trigger receptors A and B Odorant 6 can trigger receptors B and C and odorant 7 can trigger receptor B. Conversely, receptor A can be triggered by odorants 1, 4 and 5 receptor B by odorants 2, 5, 6 and 7 and receptor C by odorants 3, 4 and 6.

Explain how scientists grew to suspect that G proteins are involved with olfaction. Furthermore, explain how we know there are hundreds of different odorant receptors (OR) in humans. 

There are three problems in particular that complicate interpretation of much of the data on structure-activity relations in olfaction. First, the different techniques used often yield data that are not strictly comparable. Recordings from a single or a few receptors, for example, are more reliable indicators of the odorant-receptor interaction than are recordings of the massed action of many neural elements in the olfactory bulb. 

The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. It is accepted that the sensation of odor is triggered by highly complex mixtures of volatile molecules, mostly hydrophobic, and usually occurring in trace-level concentrations (ppm or ppb). These volatiles interact with odorant receptors of the olfactive epithelium located in the nasal cavity. Once the receptor is activated, a cascade of events is triggered to transform the chemical-structural information contained in the odorous stimulus into a membrane potential [58,59], which is projected to the olfactory bulb and then transported to higher regions of the brain [60] where the translation occurs. 

Di Natale C, Martinelli E, Paolesse R, D Amico A, Pilippini D, Lundstrom I (2008) An experimental biomimetic platform for artificial olfaction. PLoS ONE 3 e3139 Mombaerts P (1999) Molecular biology of odorant receptors in vertebrates. Aimu Rev Neurosci 22 487-509... 

According to the chemical theory of olfaction, the mechanism by which olfaction occurs is the emittance of particles by the odorous substances. These particles are conveyed to the olfactory epithelium by convection, diffusion, or both, and dkecdy or indkectly induce chemical changes in the olfactory receptors. 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

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