Heteromer

A heteromer is something that consists of different parts; the antonym of homomeric. Examples are:

Biology

  • Spinal neurons that pass over to the opposite side of the spinal cord.[1]
  • A protein complex that contains two or more different polypeptides.[2]

Pharmacology

  • Ligand-gated ion channels such as the nicotinic acetylcholine receptor and GABAA receptor are composed of five subunits arranged around a central pore that opens to allow ions to pass through. There are many different subunits available that can come together in a wide variety of combinations to form different subtypes of the ion channel.[3][4][5] Sometimes the channel can be made from only one type of subunit, such as the α7 nicotinic receptor, which is made up from five α7 subunits, and so is a homomer rather than a heteromer, but more commonly several different types of subunit will come together to form a heteromeric complex (e.g., the α4β2 nicotinic receptor, which is made up from two α4 subunits and three β2 subunits). Because the different ion channel subtypes are expressed to different extents in different tissues, this allows selective modulation of ion transport and means that a single neurotransmitter can produce varying effects depending on where in the body it is released.[6][7][8]
  • G protein-coupled receptors are composed of seven membrane-spanning alpha-helical segments that are usually linked together into a single folded chain to form the receptor complex. However, research has demonstrated that a number of GPCRs are also capable of forming heteromers from a combination of two or more individual GPCR subunits under some circumstances, especially where several different GPCRs are densely expressed in the same neuron. Such heteromers may be between receptors from the same family (e.g., adenosine A1/A2A heteromers[9][10] and dopamine D1/D2[11] and D1/D3 heteromers[12]) or between entirely unrelated receptors such as CB1/A2A,[13] glutamate mGluR5 / adenosine A2A heteromers,[14] cannabinoid CB1 / dopamine D2 heteromers,[15] and even CB1/A2A/D2 heterotrimers where three different receptors have come together to form a heteromer.[16][17] The ligand binding properties and intracellular trafficking pathways of GPCR heteromers usually show elements from both parent receptors, but may also produce quite unexpected pharmacological effects, making such heteromers an important focus of current research.[18][19][20][21][22]

See also

  • GPCR oligomer

References

  1. ↑ Medical dictionary
  2. ↑ Merriam-Webster Dictionary
  3. ↑ Gotti C, Moretti M, Gaimarri A, Zanardi A, Clementi F, Zoli M (October 2007). "Heterogeneity and complexity of native brain nicotinic receptors". Biochemical Pharmacology. 74 (8): 1102–11. doi:10.1016/j.bcp.2007.05.023. PMID 17597586.
  4. ↑ Millar NS, Gotti C (January 2009). "Diversity of vertebrate nicotinic acetylcholine receptors". Neuropharmacology. 56 (1): 237–46. doi:10.1016/j.neuropharm.2008.07.041. PMID 18723036. S2CID 27181755.
  5. ↑ Collins AC, Salminen O, Marks MJ, Whiteaker P, Grady SR (2009). "The road to discovery of neuronal nicotinic cholinergic receptor subtypes". Nicotine Psychopharmacology. Handbook of Experimental Pharmacology. Vol. 192. pp. 85–112. doi:10.1007/978-3-540-69248-5_4. ISBN 978-3-540-69246-1. PMID 19184647.
  6. ↑ Graham AJ, Martin-Ruiz CM, Teaktong T, Ray MA, Court JA (August 2002). "Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders". Current Drug Targets. CNS and Neurological Disorders. 1 (4): 387–97. doi:10.2174/1568007023339283. PMID 12769611.
  7. ↑ Nutt D (April 2006). "GABAA receptors: subtypes, regional distribution, and function". Journal of Clinical Sleep Medicine. 2 (2): S7–11. doi:10.5664/jcsm.26525. PMID 17557501.
  8. ↑ Heldt SA, Ressler KJ (December 2007). "Forebrain and midbrain distribution of major benzodiazepine–sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization". Neuroscience. 150 (2): 370–85. doi:10.1016/j.neuroscience.2007.09.008. PMC 2292345. PMID 17950542.
  9. ↑ Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R (February 2006). "Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers". Journal of Neuroscience. 26 (7): 2080–7. doi:10.1523/JNEUROSCI.3574-05.2006. PMC 6674939. PMID 16481441.
  10. ↑ Ferre S, Ciruela F, Borycz J, Solinas M, Quarta D, Antoniou K, Quiroz C, Justinova Z, Lluis C, Franco R, Goldberg SR (2008). "Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain". Frontiers in Bioscience. 13 (13): 2391–9. doi:10.2741/2852. PMID 17981720.
  11. ↑ Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, O'Dowd BF, George SR (January 2007). "D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum". Proceedings of the National Academy of Sciences of the United States of America. 104 (2): 654–9. Bibcode:2007PNAS..104..654R. doi:10.1073/pnas.0604049104. PMC 1766439. PMID 17194762.
  12. ↑ Marcellino D, Ferré S, Casadó V, Cortés A, Le Foll B, Mazzola C, Drago F, Saur O, Stark H, Soriano A, Barnes C, Goldberg SR, Lluis C, Fuxe K, Franco R (September 2008). "Identification of Dopamine D1–D3 Receptor Heteromers: INDICATIONS FOR A ROLE OF SYNERGISTIC D1–D3 RECEPTOR INTERACTIONS IN THE STRIATUM". The Journal of Biological Chemistry. 283 (38): 26016–25. doi:10.1074/jbc.M710349200. PMC 2533781. PMID 18644790.
  13. ↑ Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, Müller C, Woods AS, Hope BT, Ciruela F, Casadó V, Canela EI, Lluis C, Goldberg SR, Moratalla R, Franco R, Ferré S (2007). "Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids". Neuropsychopharmacology. 32 (11): 2249–59. doi:10.1038/sj.npp.1301375. PMID 17356572.
  14. ↑ Zezula J, Freissmuth M (March 2008). "The A2A-adenosine receptor: a GPCR with unique features?". British Journal of Pharmacology. 153 Suppl 1 (S1): S184–90. doi:10.1038/sj.bjp.0707674. PMC 2268059. PMID 18246094.
  15. ↑ Marcellino D, Carriba P, Filip M, Borgkvist A, Frankowska M, Bellido I, Tanganelli S, Müller CE, Fisone G, Lluis C, Agnati LF, Franco R, Fuxe K (April 2008). "Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis". Neuropharmacology. 54 (5): 815–23. doi:10.1016/j.neuropharm.2007.12.011. PMID 18262573. S2CID 195685369.
  16. ↑ Carriba P, Navarro G, Ciruela F, Ferré S, Casadó V, Agnati L, Cortés A, Mallol J, Fuxe K, Canela EI, Lluis C, Franco R (2008). "Detection of heteromerization of more than two proteins by sequential BRET-FRET". Nature Methods. 5 (8): 727–33. doi:10.1038/nmeth.1229. PMID 18587404. S2CID 5175118.
  17. ↑ Ferré S, Goldberg SR, Lluis C, Franco R (2009). "Looking for the role of cannabinoid receptor heteromers in striatal function". Neuropharmacology. 56 Suppl 1 (Suppl 1): 226–34. doi:10.1016/j.neuropharm.2008.06.076. PMC 2635338. PMID 18691604.
  18. ↑ Franco R, Casadó V, Cortés A, Mallol J, Ciruela F, Ferré S, Lluis C, Canela EI (March 2008). "G-protein-coupled receptor heteromers: function and ligand pharmacology". British Journal of Pharmacology. 153 Suppl 1 (S1): S90–8. doi:10.1038/sj.bjp.0707571. PMC 2268068. PMID 18037920.
  19. ↑ Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago B, Roberts DC, Langel U, Genedani S, Ferraro L, de la Calle A, Narvaez J, Tanganelli S, Woods A, Agnati LF (August 2008). "Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology". Brain Research Reviews. 58 (2): 415–52. doi:10.1016/j.brainresrev.2007.11.007. PMID 18222544. S2CID 206344737.
  20. ↑ Franco R, Casadó V, Cortés A, Pérez-Capote K, Mallol J, Canela E, Ferré S, Lluis C (August 2008). "Novel pharmacological targets based on receptor heteromers". Brain Research Reviews. 58 (2): 475–82. doi:10.1016/j.brainresrev.2008.06.002. PMID 18620000. S2CID 41153163.
  21. ↑ Fuxe K, Marcellino D, Woods AS, Giuseppina L, Antonelli T, Ferraro L, Tanganelli S, Agnati LF (January 2009). "Integrated signaling in heterodimers and receptor mosaics of different types of GPCRs of the forebrain: relevance for schizophrenia". Journal of Neural Transmission. 116 (8): 923–39. doi:10.1007/s00702-008-0174-9. PMC 2953764. PMID 19156349.
  22. ↑ Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KD, Pin JP, Volkow ND, Waldhoer M, Woods AS, Franco R (March 2009). "Building a new conceptual framework for receptor heteromers". Nature Chemical Biology. 5 (3): 131–4. doi:10.1038/nchembio0309-131. PMC 2681085. PMID 19219011.
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