Otopetrin family explained

Symbol:Otopetrin
Otopetrin
Width:500
Pfam:PF03189
Pdb:6NF4, 6NF6
Interpro:IPR004878
Tcdb:1.A.110
Opm Family: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,[1] and were later shown to form proton-selective ion channels expressed in many different tissues, including taste receptor cells.[2] 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).[3] Recently the structures of OTOP1 and OTOP3 were solved by CryoEM, which showed that the protein assembles as a dimer.[4] [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.[6]

Otopetrins were initially thought to modulate calcium homeostasis and influx of calcium in response to extracellular ATP[7] but were subsequently shown to form proton-selective ion channels.

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.[7] [8] [9]

OTOP1 was identified as a candidate for the sour receptor in mice in 2018 and its function as a sour receptor was confirmed in subsequent studies.[10] [11] Despite serving as a sour taste receptor, OTOP1 is not essential for mice to respond to and avoid sour tastes.

Further reading

Notes and References

  1. 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. 10.1093/hmg/ddg087. 12651873. free.
  2. 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. 10.1126/science.aao3264. 5845439. 29371428. 2018Sci...359.1047T.
  3. Hughes I, Binkley J, Hurle B, Green ED, Sidow A, Ornitz DM . Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members . BMC Evolutionary Biology . 8 . 41 . February 2008 . 1 . 18254951 . 2268672 . 10.1186/1471-2148-8-41 . 2008BMCEE...8...41H . free .
  4. Saotome K, Teng B, ((Tsui CCA)), Lee WH, Tu YH, Kaplan JP, ((Sansom MSP)), Liman ER, Ward AB . Structures of the otopetrin proton channels Otop1 and Otop3 . Nat Struct Mol Biol . 26 . 518–525 . June 2019 . 6 . 31160780 . 6564688 . 10.1038/s41594-019-0235-9 .
  5. Chen Q, Zeng W, She J, Bai XC, Jiang Y . Structural and functional characterization of an otopetrin family proton channel . eLife . 8 . e46710 . April 2019 . 30973323 . 6483595 . 10.7554/eLife.46710 . free .
  6. Saotome K, Teng B, ((Tsui CCA)), Lee WH, Tu YH, Kaplan JP, ((Sansom MSP)), Liman ER, Ward AB . Structures of the otopetrin proton channels Otop1 and Otop3 . Nat Struct Mol Biol . 26 . 518–525 . June 2019 . 6 . 31160780 . 6564688 . 10.1038/s41594-019-0235-9 .
  7. Hughes I, Saito M, Schlesinger PH, Ornitz DM . 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 . July 2007 . 17606897 . 1924595 . 10.1073/pnas.0705182104 . 2007PNAS..10412023H . free .
  8. Söllner C, Schwarz H, Geisler R, Nicolson T . Mutated otopetrin 1 affects the genesis of otoliths and the localization of Starmaker in zebrafish . Development Genes and Evolution . 214 . 12 . 582–90 . December 2004 . 15480759 . 10.1007/s00427-004-0440-2 . 1581286 .
  9. Hughes I, Blasiole B, Huss D, Warchol ME, Rath NP, Hurle B, Ignatova E, Dickman JD, Thalmann R, Levenson R, Ornitz DM . Otopetrin 1 is required for otolith formation in the zebrafish Danio rerio . Developmental Biology . 276 . 2 . 391–402 . December 2004 . 15581873 . 2522322 . 10.1016/j.ydbio.2004.09.001 .
  10. 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. 10.1016/j.cub.2019.08.077. 31543453. 7299528. free.
  11. 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. 10.1016/j.cell.2019.08.031. 31543264. free.

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