Olfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain. These receptors are members of the class A rhodopsin-like family of G protein-coupled receptors (GPCRs).^[1]

Expression

In vertebrates, the olfactory receptors are located in the cilia of the olfactory sensory neurons.^[2] In insects, olfactory receptors are located on the antennae and other chemosensory organs.^[3] Sperm cells also express odor receptors, which are thought to be involved in chemotaxis to find the egg cell.^[4]

Mechanism

Rather than binding specific ligands like most receptors, olfactory receptors display affinity for a range of odor molecules and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities.^[5] Once the odorant has bound to the odor receptor, the receptor undergoes structural changes and it binds and activates the olfactory-type G protein on the inside of the olfactory receptor neuron. The G protein (G_olf and/or G_s)^[6] in turn activates the lyase - adenylate cyclase - which converts ATP into cyclic AMP (cAMP). The cAMP opens cyclic nucleotide-gated ion channels which allow calcium and sodium ions to enter into the cell, depolarizing the olfactory receptor neuron and beginning an action potential which carries the information to the brain.

Diversity

There are a wide range of different odor receptors, with as many as 1,000 in the mammalian genome which represents approximately 3% of the genes in the genome. However not all of these potential odor receptor genes are expressed and are functional. According to an analysis of data derived from the human genome project, humans have approximately 400 functional genes coding for olfactory receptors and the remaining 600 candidates are pseudogenes.^[7]

The reason for the large number of different odor receptors is to provide a system for discriminating between as many different odors as possible. Even so, each odor receptor does not detect a single odor. Rather each individual odor receptor is broadly tuned to be activated by a number of similar odorant structures.^[8][9] Analogous to the immune system, the diversity that exists within the olfactory receptor family allows molecules that have never been encountered before to be characterized. However, unlike the immune system, which generates diversity through in-situ recombination, every single olfactory receptor is translated from a specific gene; hence the large portion of the genome devoted to encoding OR genes. Furthermore most odors activate more than one type of odor receptor. Since the number of combinations and permutations of olfactory receptors is almost limitless, the olfactory receptor system is capable of detecting and distinguishing between a practically infinite number of odorant molecules.

Families

A nomenclature system has been devised for the olfactory receptor family^[10] and is the basis for the official Human Genome Project (HUGO) symbols for the genes that encode these receptors. The names of individual olfactory receptor family members are in the format "ORnXm" where:

• OR is the root name (Olfactory Receptor superfamily)
• n = an integer representing a family (e.g., 1-56) whose members have greater than 40% sequence identity,
• X = a single letter (A, B, C, ...) denoting a subfamily (>60% sequence identity), and
• m = an integer representing an individual family member (isoform).

For example is the first isoform of subfamily A of olfactory receptor family 1.

Members belonging to the same subfamily of olfactory receptors (>60% sequence identity) are likely to recognize structurally similar odorant molecules.^[11]

Two major classes of olfactory receptors have been identified in humans:^[12]

• class I (fish-like receptors) OR families 51-56
• class II (tetrapod specific receptors) OR families 1-13

Discovery

In 2004 Linda B. Buck and Richard Axel won the Nobel Prize in Physiology or Medicine for their work on olfactory receptors.^[13][14] In 2006 it was shown that another class of odorant receptors exist for volatile amines.^[15] This class of receptors consists of the trace amine-associated receptors (TAAR) with the exception of TAAR1 which is a receptor for thyronamines.

Unfortunately, as with many other GPCRs, there is still a lack of experimental structures at atomic level for olfactory receptors and structural information is based on homology modeling methods.^[16]

See also

• Receptor
• Trace amine-associated receptor
• Odorant

References

External links

• Olfactory Receptor Database
• Human Olfactory Receptor Data Exploratorium (HORDE)

de:Geruchsrezeptor (Protein) fr:Récepteurs olfactifs lt:Kvapo receptoriai ja:????? zh:????