TRPN

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TRPN is a member of the transient receptor potential channel family of ion channels, which is a diverse group of proteins thought to be involved in mechanoreception.[1] The TRPN gene was given the name no mechanoreceptor potential C (nompC) when it was first discovered in fruit flies,[2] hence the N in TRPN. Since its discovery in fruit flies, TRPN homologs have been discovered and characterized in worms,[3] frogs,[4] and zebrafish.[5]

Structure

A structure of NOMPC was published in 2017, solved using electron cryo-microscopy.[6] X-ray crystallography studies of channel segments cloned from fruit flies and zebrafish have led to the hypothesis that multiple ankyrin repeats at TRPN's N-terminus are involved in the gating of the channel pore.[7] Crystallography studies of TRPY1, a yeast TRP homolog,[8] have shown that aromatic residues conserved across TRP family members, including TRPN, in the sixth transmembrane domain are critical to the gating mechanism as well.[7]

Function

As a mechanoreceptor, TRPN responds to impinging mechanical forces. Studies in TRPN deficient adult fruit flies and larvae have shown that these null mutants have severe difficulty moving, which suggests a role for TRPN in proprioception.[9] This hypothesis is further strengthened by immunostaining studies in fruit flies that have shown TRPN localization in the cilia of campaniform sensilla and chordotonal organs in Johnston's organ.[10] Further immunostaining studies in fruit flies have identified, with higher resolution techniques, that TRPN is localized at the distal end of motile mechanosensory cilia in Johnston's organ.[11] However, TRPN is not required for transduction of mechanical stimuli in larvae[12] or adult flies,[13] suggesting that the TRPV channels nanchung and inactive may also serve a mechanosensory function.[13]

Studies in worms have shown that TRPN mutants have locomotion defects, as well as a decreased basal slowing response, which is a reduction in rate of motion that is induced by contact with a food source.[3] This result further strengthens the hypothesis that TRPN is vital to proprioception. Electrophysiological studies of single channels in worms have shown that TRPN responds to mechanical stimuli and has a preference for sodium ions,[14] although a complete ion selectivity profile has yet to be identified.

Studies in zebrafish larvae have also shown that morpholino-mediated knockdown of TRPN function result in deafness as well as imbalance,[5] suggesting a dual role in hearing as well as proprioception. Immunostaining studies in frog embryos have shown localization of TRPN at the tips of mechanosensory cilia in the lateral line, hair cells and ciliated epidermal cells,[4] suggesting a role in a variety of mechanosensory functions. TRPN localizes to the kinocilia, not stereocilia, of amphibian hair cells, suggesting the presence of two distinct classes of mechanosensitive channel.

TRPN has the capability of performing a variety of roles in mechanosensory systems.[citation needed]

Genes

Genomic data from a variety of organisms show that TRPN is present in most animals, but it is absent in all amniotes.[15] In most animals the number of ankyrin repeats is between 28 and 29.

The following is a list of genes encoding TRPN organized by the organism in which they are found. Gene names are specific to the organism and to the way in which they were discovered, which is why the gene name may not explicitly be "TRPN". Links to the NCBI Gene database are included whenever possible.

Fruit fly (Drosophila melanogaster)

Nematode worm (Caenorhabditis elegans)

African clawed frog (Xenopus laevis)

Zebrafish (Danio rerio)

References

  1. ^ Duggan, A.; García-Añoveros, J.; Corey, D. P. (2000). "Insect mechanoreception: What a long, strange TRP it's been". Current Biology. 10 (10): R384–R387. doi:10.1016/s0960-9822(00)00478-4. PMID 10837217.
  2. ^ Walker, R. G.; Willingham, A. T.; Zuker, C. S. (2000). "A Drosophila mechanosensory transduction channel". Science. 287 (5461): 2229–2234. CiteSeerX 10.1.1.646.2497. doi:10.1126/science.287.5461.2229. PMID 10744543.
  3. ^ a b Li, W.; Feng, Z.; Sternberg, P. W.; Shawn Xu, X. Z. (2006). "A C. Elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue". Nature. 440 (7084): 684–687. doi:10.1038/nature04538. PMC 2865900. PMID 16572173.
  4. ^ a b Shin, J. -B.; Adams, D.; Paukert, M.; Siba, M.; Sidi, S.; Levin, M.; Gillespie, P. G.; Gründer, S. (2005). "Xenopus TRPN1 (NOMPC) localizes to microtubule-based cilia in epithelial cells, including inner-ear hair cells". Proceedings of the National Academy of Sciences. 102 (35): 12572–12577. doi:10.1073/pnas.0502403102. PMC 1194908. PMID 16116094.
  5. ^ a b Sidi, S.; Friedrich, R. W.; Nicolson, T. (2003). "NompC TRP Channel Required for Vertebrate Sensory Hair Cell Mechanotransduction". Science. 301 (5629): 96–99. doi:10.1126/science.1084370. PMID 12805553. S2CID 23882972.
  6. ^ Jin, Peng; Bulkley, David; Guo, Yanmeng; Zhang, Wei; Guo, Zhenhao; Huynh, Walter; Wu, Shenping; Meltzer, Shan; Cheng, Tong (July 2017). "Electron cryo-microscopy structure of the mechanotransduction channel NOMPC". Nature. 547 (7661): 118–122. doi:10.1038/nature22981. ISSN 1476-4687. PMC 5669069. PMID 28658211.
  7. ^ a b Howard, J.; Bechstedt, S. (2004). "Hypothesis: A helix of ankyrin repeats of the NOMPC-TRP ion channel is the gating spring of mechanoreceptors". Current Biology. 14 (6): R224–R226. doi:10.1016/j.cub.2004.02.050. PMID 15043829.
  8. ^ Palmer, C. P.; Zhou, X. L.; Lin, J.; Loukin, S. H.; Kung, C.; Saimi, Y. (2001). "A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca2+-permeable channel in the yeast vacuolar membrane". Proceedings of the National Academy of Sciences. 98 (14): 7801–7805. doi:10.1073/pnas.141036198. PMC 35422. PMID 11427713.
  9. ^ Cheng, L. E.; Song, W.; Looger, L. L.; Jan, L. Y.; Jan, Y. N. (2010). "The role of the TRP channel NompC in Drosophila larval and adult locomotion". Neuron. 67 (3): 373–380. doi:10.1016/j.neuron.2010.07.004. PMC 2933178. PMID 20696376.
  10. ^ Liang, X.; Madrid, J.; Saleh, H. S.; Howard, J. (2011). "NOMPC, a Member of the TRP Channel Family, Localizes to the Tubular Body and Distal Cilium of Drosophila Campaniform and Chordotonal Receptor Cells". Cytoskeleton. 68 (1): 1–7. doi:10.1002/cm.20493. PMC 3048163. PMID 21069788.
  11. ^ Lee, J.; Moon, S.; Cha, Y.; Chung, Y. D. (2010). Gonzalez, Cayetano (ed.). "Drosophila TRPN( =NOMPC) Channel Localizes to the Distal End of Mechanosensory Cilia". PLOS ONE. 5 (6): e11012. doi:10.1371/journal.pone.0011012. PMC 2882365. PMID 20543979.
  12. ^ Zhang, W; Yan, Z; Jan, L. Y.; Jan, Y. N. (2013). "Sound response mediated by the TRP channels NOMPC, NANCHUNG, and INACTIVE in chordotonal organs of Drosophila larvae". Proceedings of the National Academy of Sciences. 110 (33): 13612–7. doi:10.1073/pnas.1312477110. PMC 3746866. PMID 23898199.
  13. ^ a b Lehnert, B. P.; Baker, A. E.; Gaudry, Q; Chiang, A. S.; Wilson, R. I. (2013). "Distinct roles of TRP channels in auditory transduction and amplification in Drosophila". Neuron. 77 (1): 115–28. doi:10.1016/j.neuron.2012.11.030. PMC 3811118. PMID 23312520.
  14. ^ Kang, L.; Gao, J.; Schafer, W. R.; Xie, Z.; Xu, X. Z. S. (2010). "C. Elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel". Neuron. 67 (3): 381–391. doi:10.1016/j.neuron.2010.06.032. PMC 2928144. PMID 20696377.
  15. ^ Schüler, Andreas; Schmitz, Gregor; Reft, Abigail; Özbek, Suat; Thurm, Ulrich; Bornberg-Bauer, Erich (June 2015). "The Rise and Fall of TRP-N, an Ancient Family of Mechanogated Ion Channels, in Metazoa". Genome Biology and Evolution. 7 (6): 1713–1727. doi:10.1093/gbe/evv091. PMC 4494053. PMID 26100409.
  16. ^ NCBI Genbank entry
  17. ^ NCBI Genbank entry
  18. ^ NCBI Genbank entry
  19. ^ NCBI Genbank entry
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