dTULP, the Homolog of Tubby, Regulates Transient Receptor Potential Channel Localization in Cilia

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Mechanically gated ion channels convert sound into an electrical signal for the sense of hearing. In Drosophila melanogaster, several transient receptor potential (TRP) channels have been implicated to be involved in this process. TRPN (NompC) and TRPV (Inactive) channels are localized in the distal and proximal ciliary zones of auditory receptor neurons, respectively. This segregated ciliary localization suggests distinct roles in auditory transduction. However, the regulation of this localization is not fully understood. Here we show that the Drosophila Tubby homolog, King tubby (hereafter called dTULP) regulates ciliary localization of TRPs. dTULP-deficient flies show uncoordinated movement and complete loss of sound-evoked action potentials. Inactive and NompC are mislocalized in the cilia of auditory receptor neurons in the dTulp mutants, indicating that dTULP is required for proper cilia membrane protein localization. This is the first demonstration that dTULP regulates TRP channel localization in cilia, and suggests that dTULP is a protein that regulates ciliary neurosensory functions.

Vyšlo v časopise: dTULP, the Homolog of Tubby, Regulates Transient Receptor Potential Channel Localization in Cilia. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003814
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003814

Souhrn

Zdroje

1. HudspethAJ (1992) Hair-bundle mechanics and a model for mechanoelectrical transduction by hair cells. Soc Gen Physiol Ser 47: 357–370.

2. GillespiePG, MullerU (2009) Mechanotransduction by hair cells: models, molecules, and mechanisms. Cell 139: 33–44.

3. LuQ, SenthilanPR, EffertzT, NadrowskiB, GopfertMC (2009) Using Drosophila for studying fundamental processes in hearing. Integr Comp Biol 49: 674–680.

4. EberlDF, HardyRW, KernanMJ (2000) Genetically similar transduction mechanisms for touch and hearing in Drosophila. J Neurosci 20: 5981–5988.

5. GreenspanRJ, FerveurJF (2000) Courtship in Drosophila. Annu Rev Genet 34: 205–232.

6. HallJC (1994) The mating of a fly. Science 264: 1702–1714.

7. Von SchilcherF (1976) The behavior of cacophony, a courtship song mutant in Drosophila melanogaster. Behav Biol 17: 187–196.

8. EberlDF, DuykGM, PerrimonN (1997) A genetic screen for mutations that disrupt an auditory response in Drosophila melanogaster. Proc Natl Acad Sci U S A 94: 14837–14842.

9. GopfertMC, RobertD (2001) Biomechanics. Turning the key on Drosophila audition. Nature 411: 908.

10. EffertzT, WiekR, GopfertMC (2011) NompC TRP channel is essential for Drosophila sound receptor function. Curr Biol 21: 592–597.

11. GongZ, SonW, ChungYD, KimJ, ShinDW, et al. (2004) Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila. J Neurosci 24: 9059–9066.

12. GopfertMC, AlbertJT, NadrowskiB, KamikouchiA (2006) Specification of auditory sensitivity by Drosophila TRP channels. Nat Neurosci 9: 999–1000.

13. KimJ, ChungYD, ParkDY, ChoiS, ShinDW, et al. (2003) A TRPV family ion channel required for hearing in Drosophila. Nature 424: 81–84.

14. LehnertBP, BakerAE, GaudryQ, ChiangAS, WilsonRI (2013) Distinct roles of TRP channels in auditory transduction and amplification in Drosophila. Neuron 77: 115–128.

15. KangL, GaoJ, SchaferWR, XieZ, XuXZ (2010) C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel. Neuron 67: 381–391.

16. YanZ, ZhangW, HeY, GorczycaD, XiangY, et al. (2013) Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature 493: 221–225.

17. LeeJ, MoonS, ChaY, ChungYD (2010) Drosophila TRPN( = NOMPC) channel localizes to the distal end of mechanosensory cilia. PLoS One 5: e11012.

18. LiangX, MadridJ, SalehHS, HowardJ (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 (Hoboken) 68: 1–7.

19. BechstedtS, AlbertJT, KreilDP, Muller-ReichertT, GopfertMC, et al. (2010) A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia. Nat Commun 1: 11.

20. CacheroS, SimpsonTI, Zur LagePI, MaL, NewtonFG, et al. (2011) The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons. PLoS Biol 9: e1000568.

21. SenthilanPR, PiepenbrockD, OvezmyradovG, NadrowskiB, BechstedtS, et al. (2012) Drosophila auditory organ genes and genetic hearing defects. Cell 150: 1042–1054.

22. LaurenconA, DubruilleR, EfimenkoE, GrenierG, BissettR, et al. (2007) Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species. Genome Biol 8: R195.

23. LeeE, Sivan-LoukianovaE, EberlDF, KernanMJ (2008) An IFT-A protein is required to delimit functionally distinct zones in mechanosensory cilia. Curr Biol 18: 1899–1906.

24. ColeDG, DienerDR, HimelblauAL, BeechPL, FusterJC, et al. (1998) Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J Cell Biol 141: 993–1008.

25. PazourGJ, WilkersonCG, WitmanGB (1998) A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). J Cell Biol 141: 979–992.

26. ScholeyJM, AndersonKV (2006) Intraflagellar transport and cilium-based signaling. Cell 125: 439–442.

27. NorthMA, NaggertJK, YanY, Noben-TrauthK, NishinaPM (1997) Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases. Proc Natl Acad Sci U S A 94: 3128–3133.

28. RonshaugenM, McGinnisN, InglisD, ChouD, ZhaoJ, et al. (2002) Structure and expression patterns of Drosophila TULP and TUSP, members of the tubby-like gene family. Mech Dev 117: 209–215.

29. GongWJ, GolicKG (2003) Ends-out, or replacement, gene targeting in Drosophila. Proc Natl Acad Sci U S A 100: 2556–2561.

30. VenkenKJ, HeY, HoskinsRA, BellenHJ (2006) P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747–1751.

31. ChengLE, SongW, LoogerLL, JanLY, JanYN (2010) The role of the TRP channel NompC in Drosophila larval and adult locomotion. Neuron 67: 373–380.

32. SantagataS, BoggonTJ, BairdCL, GomezCA, ZhaoJ, et al. (2001) G-protein signaling through tubby proteins. Science 292: 2041–2050.

33. ChungYD, ZhuJ, HanY, KernanMJ (2001) nompA encodes a PNS-specific, ZP domain protein required to connect mechanosensory dendrites to sensory structures. Neuron 29: 415–428.

34. CookB, HardyRW, McConnaugheyWB, ZukerCS (2008) Preserving cell shape under environmental stress. Nature 452: 361–364.

35. HusainN, PellikkaM, HongH, KlimentovaT, ChoeKM, et al. (2006) The agrin/perlecan-related protein eyes shut is essential for epithelial lumen formation in the Drosophila retina. Dev Cell 11: 483–493.

36. HanYG, KwokBH, KernanMJ (2003) Intraflagellar transport is required in Drosophila to differentiate sensory cilia but not sperm. Curr Biol 13: 1679–1686.

37. MukhopadhyayS, WenX, ChihB, NelsonCD, LaneWS, et al. (2010) TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes Dev 24: 2180–2193.

38. BischofJ, MaedaRK, HedigerM, KarchF, BaslerK (2007) An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc Natl Acad Sci U S A 104: 3312–3317.

39. BoggonTJ, ShanWS, SantagataS, MyersSC, ShapiroL (1999) Implication of tubby proteins as transcription factors by structure-based functional analysis. Science 286: 2119–2125.

40. CaberoyNB, ZhouY, LiW (2010) Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J 29: 3898–3910.

41. KapellerR, MoriartyA, StraussA, StubdalH, TheriaultK, et al. (1999) Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin. J Biol Chem 274: 24980–24986.

42. MukhopadhyayA, DeplanckeB, WalhoutAJ, TissenbaumHA (2005) C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2: 35–42.

43. MukhopadhyayA, PanX, LambrightDG, TissenbaumHA (2007) An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Rep 8: 931–938.

44. GreenJS, ParfreyPS, HarnettJD, FaridNR, CramerBC, et al. (1989) The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med 321: 1002–1009.

45. VernonM (1969) Usher's syndrome–deafness and progressive blindness. Clinical cases, prevention, theory and literature survey. J Chronic Dis 22: 133–151.

46. ArdenGB, FoxB (1979) Increased incidence of abnormal nasal cilia in patients with retinitis pigmentosa. Nature 279: 534–536.

47. SunX, HaleyJ, BulgakovolegOV, CaiX, McGinnisJ, et al. (2012) Tubby is required for trafficking g protein-coupled receptors to neuronal cilia. Cilia 1: 21.

48. HagstromSA, AdamianM, ScimecaM, PawlykBS, YueG, et al. (2001) A role for the Tubby-like protein 1 in rhodopsin transport. Invest Ophthalmol Vis Sci 42: 1955–1962.

49. MukhopadhyayS, WenX, RattiN, LoktevA, RangellL, et al. (2013) The Ciliary G-Protein-Coupled Receptor Gpr161 Negatively Regulates the Sonic Hedgehog Pathway via cAMP Signaling. Cell 152: 210–223.

50. ChenSF, TsaiYC, FanSS (2012) Drosophila king tubby (ktub) mediates light-induced rhodopsin endocytosis and retinal degeneration. J Biomed Sci 19: 101.

51. MoonSJ, LeeY, JiaoY, MontellC (2009) A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship. Curr Biol 19: 1623–1627.