Otopetrin family
| Otopetrin | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||||
| Symbol | Otopetrin | ||||||||||
| Pfam | PF03189 | ||||||||||
| InterPro | IPR004878 | ||||||||||
| TCDB | 1.A.110 | ||||||||||
| OPM superfamily | 545 | ||||||||||
| OPM protein | 6o84 | ||||||||||
| |||||||||||
The otopetrin family is a group of proteins that were first identified based on their essential role in the vestibular system,[2] and were later shown to form proton-selective ion channels expressed in many different tissues, including taste receptor cells.[3] They are named after the Greek word "o̱tós," which means ear and "pétrā," which means rock, in reference to their role in the formation of otoconia/otoliths in the inner ear.
The structure of otopetrin-1 (OTOP1) was predicted to include 12 transmembrane domains, with three conserved sub-domains (OD-1 to OD-III).[4] Recently the structures of OTOP1 and OTOP3 were solved by CryoEM, which showed that the protein assembles as a dimer.[1][5] The first six transmembrane domains (N-terminal domain) and the second six transmembrane domains (C-terminal) share structural similarity, such that the assembled channel adopts a pseudotetrameric stoichiometry. A permeation pathway for ions is not clear in the solved structures, which show that the central cavity is filled with lipids. Molecular dynamic simulations show that protons may permeate the channel through the N terminal domain, C terminal domain, or the interface of the two domains.[1]
Otopetrins were initially thought to modulate calcium homeostasis and influx of calcium in response to extracellular ATP[6] but were subsequently shown to form proton-selective ion channels.[3]
Otopetrin 1 (OTOP1) is required for normal formation of otoconia/otoliths in the inner ear. Otoconia are minute biomineral particles embedded in a gelatinous membrane that overlies the sensory epithelium in the inner ear. Gravity and acceleration cause the octoconia to deflect the stereocilia of sensory hair cells. Otoconia are required for processing of information regarding spatial orientation and acceleration.[6][7][8]
OTOP1 was identified as a candidate for the sour receptor in mice in 2018 [3] and its function as a sour receptor was confirmed in subsequent studies.[9][10] Despite serving as a sour taste receptor, OTOP1 is not essential for mice to respond to and avoid sour tastes.
References
- ^ a b c Saotome K, Teng B, Tsui CCA, Lee WH, Tu YH, Kaplan JP, Sansom MSP, Liman ER, Ward AB (June 2019). "Structures of the otopetrin proton channels Otop1 and Otop3". Nat Struct Mol Biol. 26 (6): 518–525. doi:10.1038/s41594-019-0235-9. PMC 6564688. PMID 31160780.
- ^ Hurle B, Ignatova E, Massironi SM, Mashimo T, Rios X, Thalmann I, Thalmann R, Ornitz DM (April 2003). "Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1". Hum Mol Genet. 12 (7): 777–789. doi:10.1093/hmg/ddg087. PMID 12651873.
- ^ a b c Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ, Turner HN, Mulhall EM, Ye W, Smith AD, Liman ER (March 2018). "An evolutionarily conserved gene family encodes proton-selective ion channels". Science. 359 (6379): 1047–1050. Bibcode:2018Sci...359.1047T. doi:10.1126/science.aao3264. PMC 5845439. PMID 29371428.
- ^ Hughes I, Binkley J, Hurle B, Green ED, Sidow A, Ornitz DM (February 2008). "Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members". BMC Evolutionary Biology. 8 (1): 41. Bibcode:2008BMCEE...8...41H. doi:10.1186/1471-2148-8-41. PMC 2268672. PMID 18254951.
- ^ Chen Q, Zeng W, She J, Bai XC, Jiang Y (April 2019). "Structural and functional characterization of an otopetrin family proton channel". eLife. 8: e46710. doi:10.7554/eLife.46710. PMC 6483595. PMID 30973323.
- ^ a b Hughes I, Saito M, Schlesinger PH, Ornitz DM (July 2007). "Otopetrin 1 activation by purinergic nucleotides regulates intracellular calcium". Proceedings of the National Academy of Sciences of the United States of America. 104 (29): 12023–8. Bibcode:2007PNAS..10412023H. doi:10.1073/pnas.0705182104. PMC 1924595. PMID 17606897.
- ^ Söllner C, Schwarz H, Geisler R, Nicolson T (December 2004). "Mutated otopetrin 1 affects the genesis of otoliths and the localization of Starmaker in zebrafish". Development Genes and Evolution. 214 (12): 582–90. doi:10.1007/s00427-004-0440-2. PMID 15480759. S2CID 1581286.
- ^ Hughes I, Blasiole B, Huss D, Warchol ME, Rath NP, Hurle B, Ignatova E, Dickman JD, Thalmann R, Levenson R, Ornitz DM (December 2004). "Otopetrin 1 is required for otolith formation in the zebrafish Danio rerio". Developmental Biology. 276 (2): 391–402. doi:10.1016/j.ydbio.2004.09.001. PMC 2522322. PMID 15581873.
- ^ Teng B, Wilson CE, Tu YH, Joshi NR, Kinnamon SC, Liman ER (November 2019). "Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1". Current Biology. 29 (21): 3647–3656. doi:10.1016/j.cub.2019.08.077. PMC 7299528. PMID 31543453.
- ^ Zhang J, Jin H, Zhang W, Ding C, O Keeffe S, Ye M, Zuker CS (October 2019). "Sour Sensing from the Tongue to the Brain". Cell. 179 (2): 392–402. doi:10.1016/j.cell.2019.08.031. PMID 31543264.
Further reading
- Hurle B, Marques-Bonet T, Antonacci F, Hughes I, Ryan JF, Eichler EE, Ornitz DM, Green ED (January 2011). "Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses". BMC Evolutionary Biology. 11 (1): 23. Bibcode:2011BMCEE..11...23H. doi:10.1186/1471-2148-11-23. PMC 3038909. PMID 21261979.
- Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ, Turner HN, Mulhall EM, Ye W, Smith AD, Liman ER (March 2018). "An evolutionarily conserved gene family encodes proton-selective ion channels". Science. 359 (6379): 1047–1050. Bibcode:2018Sci...359.1047T. doi:10.1126/science.aao3264. PMC 5845439. PMID 29371428.