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.
Additional recommended knowledge
Expression
In vertebrates, the olfactory receptors are located in the cilia of the olfactory sensory neurons. In insects, olfactory receptors are located on the antennae. Sperm cells also express odor receptors, which are thought to be involved in chemotaxis to find the egg cell.
Function
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. 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 (Golf and/or Gs) 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.[1]
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.[2][3] 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. 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[4] 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 OR1A1 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.[5]
Two major classes of olfactory receptors have been identified in humans:[6]
- class I (fish-like receptors) OR families 51-56
- class II (tetrapod specific receptors) OR families 1-13
History and research
In 2004 Linda B. Buck and Richard Axel won the Nobel Prize in Physiology or Medicine for their work on olfactory receptors.[7][8]
In 2006 it was shown that another class of odorant receptors exist for volatile amines.[9] This class of receptors consists of the trace amine-associated receptors (TAAR) with the exception of TAAR1 which is a receptor for thyronamines.
Unfortunately, there is still a lack of experimental structures at atomic level for olfactory receptors and structural information is based on homology modeling methods.[10]
See also
References
- ^ Gilad Y, Lancet D (2003). "Population differences in the human functional olfactory repertoire". Mol. Biol. Evol. 20 (3): 307–14. doi:10.1093/molbev/msg013. PMID 12644552.
- ^ Malnic B, Hirono J, Sato T, Buck LB (1999). "Combinatorial receptor codes for odors". Cell 96 (5): 713–23. doi:10.1016/S0092-8674(00)80581-4. PMID 10089886.
- ^ Araneda RC, Peterlin Z, Zhang X, Chesler A, Firestein S (2004). "A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium". J. Physiol. (Lond.) 555 (Pt 3): 743–56. doi:10.1113/jphysiol.2003.058040. PMID 14724183.
- ^ Glusman G, Bahar A, Sharon D, Pilpel Y, White J, Lancet D (2000). "The olfactory receptor gene superfamily: data mining, classification, and nomenclature". Mamm. Genome 11 (11): 1016–23. doi:10.1007/s003350010196. PMID 11063259.
- ^ Malnic B, Godfrey PA, Buck LB (2004). "The human olfactory receptor gene family". Proc. Natl. Acad. Sci. U.S.A. 101 (8): 2584–9. doi:10.1073/pnas.0307882100. PMID 14983052.
- ^ Glusman G, Yanai I, Rubin I, Lancet D (2001). "The complete human olfactory subgenome". Genome Res. 11 (5): 685–702. doi:10.1101/gr.171001. PMID 11337468.
- ^ Buck L, Axel R (1991). "A novel multigene family may encode odorant receptors: a molecular basis for odor recognition". Cell 65 (1): 175–87. doi:10.1016/0092-8674(91)90418-X. PMID 1840504.
- ^ Press Release: The 2004 Nobel Prize in Physiology or Medicine. Retrieved on 2007-06-06.
- ^ Liberles SD, Buck LB (2006). "A second class of chemosensory receptors in the olfactory epithelium". Nature 442 (7103): 645–50. doi:10.1038/nature05066. PMID 16878137.
- ^ Khafizov K, Anselmi C, Menini A, Carloni P (2007). "Ligand specificity of odorant receptors". J Mol Model 13 (3): 401–9. doi:10.1007/s00894-006-0160-9. PMID 17120078.
| G protein-coupled receptors: olfactory receptors |
|---|
Class I
(fish-like specific receptors) |
| Family 51 |
A2 - A4 - A7 - B2 - B4 - B5 - B6 - D1 - E1 - E2 - F1 - F2 - G1 - G2 - H1 - I1 - I2 - L1 - M1 - Q1 - S1 - T1 - V1 |
| Family 52 |
A1 - A4 - A5 - B2 - B4 - B6 - D1 - E1 - E2 - E4 - E5 - E6 - E8 - H1 - I1 - I2 - J3 - K1 - K2 - L1 - L2 - M1 - N1 - N2 - N4 - N5 - P1 - R1 - W1 |
| Family 56 |
A1 - A3 - A4 - B1 - B4 |
|
|---|
Class II
(tetrapod specific receptors) |
| Family 1 |
A1 - A2 - B1 - C1 - D2 - D4 - D5 - E1 - E2 - F1 - F2 - G1 - I1 - J1 - J2 - J4 - K1 - L1 - L3 - L4 - L6 - L8 - M1 - N1 - N2 - Q1 - S1 - S2 |
| Family 2 |
A1 - A2 - A4 - A5 - A7 - A12 - A14 - A25 - A42 - AE1 - AG1 - AG2 - AJ1 - AK2 - AP1 - AT4 - B2 - B3 - B6 - B8 - B11 - C1 - C3 - D2 - D3 - F1 - F2 - G2 - G3 - G6 - H1 - H2 - J1 - J2 - J3 - K2 - L2 - L3 - L5 - L8 - L13 - M2 - M3 - M4 - M5 - M7 - N1P - S2 - T1 - T2 - T3 - T4 - T5 - T6 - T8 - T10 - T11 - T12 - T27 - T29 - T33 - T34 - T35 - V1 - V2 - W1 - W3 - W5 - Y1 - Z1 |
| Family 3 |
A1 - A2 - A3 - A4 |
| Family 4 |
A5 - A15 - A16 - A47 - B1 - C3 - C5 - C6 - C11 - C12 - C13 - C15 - C16 - C45 - C46 - D1 - D2 - D5 - D6 - D9 - D10 - D11 - E2 - F3 - F4 - F5 - F6 - F15 - F16 - F17 - F21 - F29 - K1 - K2 - K3 - K5 - K13 - K14 - K15 - K17 - L1 - M1 - M2 - N2 - N4 - N5 - P4 - Q3 - S1 - S2 - X1 - X2 |
| Family 5 |
A1 - A2 - AC2 - AK2 - AK3 - AN1 - AP2 - AR1 - AS1 - AT1 - AU1 - AY1 - B2 - B3 - B12 - B17 - B21 - BF1 - BU1 - C1 - D13 - D14 - D16 - D18 - F1 - H1 - H2 - H6 - H14 - H15 - I1 - J2 - K1 - K2 - K3 - K4 - L1 - L2 - M1 - M3 - M8 - M9 - M10 - M11 - P2 - P3 - R1 - T1 - T2 - T3 - U1 - V1 - W2 |
| Family 6 |
A2 - B1 - B2 - B3 - C1 - C2 - C3 - C4 - C6 - C65 - C68 - C70 - C74 - C75 - C76 - F1 - J1 - K2 - K3 - K6 - M1 - N1 - N2 - P1 - Q1 - S1 - T1 - V1 - X1 - Y1 |
| Family 7 |
A2 - A5 - A10 - A17 - C1 - C2 - D2 - D4 - E24 - G1 - G2 - G3 |
| Family 8 |
A1 - B2 - B3 - B4 - B8 - B12 - D1 - D2 - D4 - G1 - G2 - G5 - H1 - H2 - H3 - I2 - J1 - J3 - K1 - K3 - K5 - S1 - U1 |
| Family 9 |
A2 - A4 - G1 - G4 - I1 - K2 - Q1 - Q2 |
| Family 10 |
A2 - A3 - A4 - A5 - A6 - A7 - AD1 - AG1 - C1 - D4 - G2 - G3 - G4 - G6 - G7 - G8 - G9 - H1 - H2 - H3 - H4 - H5 - J1 - J3 - J5 - J6 - K1 - K2 - P1 - Q1 - R2 - S1 - T2 - V1 - W1 - X1 - Z1 |
| Family 11 |
A1 - G2 - H1 - H4 - H6 - L1 |
|
|---|
| Transmembrane receptor: G protein-coupled receptors |
|---|
| Class A: Rhodopsin like | Acetylcholine (M1, M2, M3, M4, M5) - Adrenergic (α1 (A, B, D), α2 (A, B, C), β1, β2, β3) - Adrenomedullin - Anaphylatoxin (C3a, C5a) - Angiotensin (1, 2) - Apelin - Bile acid - Bombesin (BRS3, GRPR, NMBR) - Bradykinin (B1, B2) - Cannabinoid (CB1, CB2) - Chemokine - Cholecystokinin (A, B) - Dopamine (D1, D2, D3, D4, D5) - Eicosanoid (CysLT (1, 2), LTB4 (1, 2), FPRL1, OXE, Prostaglandin ((DP (1, 2), EP (1, 2, 3, 4), PGF, Prostacyclin, Thromboxane) - EBI2 - Endothelin (A, B) - Estrogen - Formyl peptide (1, L1, L2) - Free fatty acid (1, 2, 3, 4) - FSH - Galanin (1, 2, 3) - Gonadotropin-releasing hormone (1, 2) - GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 182) - Ghrelin - Histamine (H1, H2, H3, H4) - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) - MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) - Melanocortin (1, 2, 3, 4, 5) - MCHR (1, 2) - Melatonin (1A, 1B)- Motilin - neuromedin (B, U (1, 2)) - Neuropeptide (B/W (1, 2), FF (1, 2), S, Y (1, 2, 4, 5)) - Neurotensin (1, 2) - Opioid (Delta, Kappa, Mu, Nociceptin, but not Sigma) - Olfactory - Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) - Orexin (1, 2) - Oxytocin - Oxoglutarate - PAF - Prokineticin (1, 2) - Prolactin-releasing peptide - Protease-activated (1, 2, 3, 4) - Purinergics (Adenosine (A1, A2a, A2b, A3), P2Y, (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)) - Relaxin (1, 2, 3, 4) - Somatostatin (1, 2, 3, 4, 5) - Serotonin, all but 5-HT3 (5-HT1 (A, B, D, E, F), 5-HT2 (A, B, C), 5-HT (4, 5A, 6, 7)) - SREB - Succinate - TAAR (1, 2, 3, 5, 6, 8, 9) - Tachykinin (1, 2, 3) - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin (1A, 1B, 2) |
|---|
| Class B: Secretin like | Brain-specific angiogenesis inhibitor (1, 2, 3) - Cadherin (1, 2, 3) - Calcitonin - CD97 - Corticotropin-releasing hormone (1, 2) - EMR (1, 2, 3) - Glucagon (GR, GIPR, GLP1R, GLP2R) - Growth hormone releasing hormone - PACAPR1- GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157) - Latrophilin (1, 2, 3, ELTD1) - Parathyroid hormone (1, 2) - Secretin - Vasoactive intestinal peptide (1, 2) |
|---|
| Class C: Metabotropic glutamate / pheromone | Calcium-sensing receptor - GABA B (1, 2) - Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) - GPRC6A - GPR (156, 158, 179) - RAIG (1, 2, 3, 4) - Taste receptors (TAS1R (1, 2, 3) TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50)) |
|---|
| Frizzled / Smoothened | Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - Smoothened |
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