Genetic Analysis of Circadian Responses to Low Frequency Electromagnetic Fields in

English version České info

Low frequency electromagnetic fields (EMFs) are associated with electrical power lines and have been implicated in the development of childhood leukemias. However, the Earth also has a natural EMF that animals can detect and which they use in order to navigate and orient themselves, particularly during migrations. One way they might do this is by using specialised photoreceptors called cryptochromes, which when activated by light, generate changes within the molecule that are susceptible to EMFs. Cryptochromes are important components of animal circadian clocks, the 24 hour timers that determine daily behavioral and physiological cycles. We have studied the circadian behavior of the fruitfly and have observed some novel and robust effects of EMFs on the fly's sleep-wake cycle that are mediated by cryptochrome. By using cryptochrome mutants we find that our results do not support the classic model for how this molecule might respond to EMFs. We also show that mammalian cryptochromes can respond to EMF when placed into transgenic Drosophila, whereas in mammalian clock neurons, they cannot. Consequently, the EMF responsiveness of cryptochrome is determined by its intracellular environment, suggesting that other, unknown molecules that interact with cryptochrome are also very important.

Vyšlo v časopise: Genetic Analysis of Circadian Responses to Low Frequency Electromagnetic Fields in. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004804
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004804

Souhrn

Zdroje

1. Kato M (2006) In: Kato M, ed. Electromagnetics in Biology. Tokyo: Springer Japan.

2. JohnsenS, LohmannKJ (2008) Magnetoreception in animals. Phys Today 61 : 29.

3. GouldJL (2010) Magnetoreception. Curr Biol 20: R431–5.

4. WiltschkoR, WiltschkoW (2013) The magnetite-based receptors in the beak of birds and their role in avian navigation. J Comp Physiol A 198 : 89–98.

5. EderSHK, CadiouH, MuhamadA, McNaughton Pa, KirschvinkJL, et al. (2012) Magnetic characterization of isolated candidate vertebrate magnetoreceptor cells. Proc Natl Acad Sci U S A 109 : 12022–12027.

6. RitzT, AdemS, SchultenK (2000) A model for photoreceptor-based magnetoreception in birds. Biophys J 78 : 707–718.

7. Solov'yovIa, ChandlerDE, SchultenK (2007) Magnetic field effects in Arabidopsis thaliana cryptochrome-1. Biophys J 92 : 2711–2726.

8. AhmadM, GallandP, RitzT, WiltschkoR, WiltschkoW (2007) Magnetic intensity affects cryptochrome-dependent responses in Arabidopsis thaliana. Planta 225 : 615–624.

9. EmeryP, StanewskyR, HallJC, RosbashM (2000) A unique circadian-rhythm photoreceptor. Nature 404 : 456–457.

10. StanewskyR, KanekoM, EmeryP, BerettaB, Wager-SmithK, et al. (1998) The cryb Mutation Identifies Cryptochrome as a Circadian Photoreceptor in Drosophila. Cell 95 : 681–692.

11. EmeryP, SoWV, KanekoM, HallJC, RosbashM (1998) CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity. Cell 95 : 669–679.

12. ZhuH, YuanQ, BriscoeAD, FroyO, CasselmanA, et al. (2005) The two CRYs of the butterfly. Curr Biol 15: R953–4.

13. YuanQ, MettervilleD, BriscoeAD, ReppertSM (2007) Insect cryptochromes: gene duplication and loss define diverse ways to construct insect circadian clocks. Mol Biol Evol 24 : 948–955.

14. KumeK, ZylkaMJ, SriramS, ShearmanLP, WeaverDR, et al. (1999) mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98 : 193–205.

15. OkamuraH, MiyakeS, SumiY, YamaguchiS, YasuiA, et al. (1999) Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science 286 : 2531–2534.

16. HoangN, SchleicherE, KacprzakS, BoulyJ (2008) Human and Drosophila cryptochromes are light activated by flavin photoreduction in living cells. PLoS Biol 6 : 1559–1569.

17. WehnerR, LabhartT (1970) Perception of the geomagnetic field in the fly Drosophila melanogaster. Experientia 967–968.

18. PhillipsJB, SayeedO (1992) Wavelength-dependent effects of light on magnetic compass in drosophila.pdf. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 172 : 303–308.

19. PainterMS, DommerDH, AltizerWW, MuheimR, PhillipsJB (2013) Spontaneous magnetic orientation in larval Drosophila shares properties with learned magnetic compass responses in adult flies and mice. J Exp Biol 216 : 1307–1316.

20. GegearR, CasselmanA, WaddellS, ReppertS (2008) Cryptochrome mediates light-dependent magnetosensitivity in Drosophila. Nature 454 : 1014–1019.

21. YoshiiT, AhmadM, Helfrich-FörsterC (2009) Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock. PLoS Biol 7: e1000086.

22. GegearRJ, FoleyLE, CasselmanA, ReppertSM (2010) Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism. Nature 463 : 804–807.

23. MüllerP, AhmadM (2011) Light-activated cryptochrome reacts with molecular oxygen to form a flavin-superoxide radical pair consistent with magnetoreception. J Biol Chem 286 : 21033–21040.

24. LeeAA, LauJCS, HogbenHJ, BiskupT, KattnigDR, et al. (2014) Alternative radical pairs for cryptochrome-based magnetoreception Alternative radical pairs for cryptochrome -⁠ based magnetoreception. J R Soc Interface 11 : 20131063.

25. FoleyLE, GegearRJ, ReppertSM (2011) Human cryptochrome exhibits light-dependent magnetosensitivity. Nat Commun 2 : 356.

26. DisselS, CoddV, FedicR, GarnerKJ, CostaR, et al. (2004) A constitutively active cryptochrome in Drosophila melanogaster. Nat Neurosci 7 : 834–840.

27. TomaDP, WhiteKP, HirschJ, GreenspanRJ (2002) Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait. Nat Genet 31 : 349–353.

28. RakshitK, GiebultowiczJM (2013) Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila. Aging Cell 12 : 752–762.

29. FedeleG, GreenEW, RosatoE, KyriacouCP (2014) An electromagnetic field disrupts negative geotaxis in Drosophila via a CRY-dependent pathway. Nat Commun 5 : 4391.

30. MarleyR, GiachelloCNG, ScruttonNS, BainesRA, JonesAR (2014) Cryptochrome-dependent magnetic field effect on seizure response in Drosophila larvae. Sci Rep 4 : 5799.

31. SchudererJ, OeschW, FelberN, SpätD, KusterN (2004) In vitro exposure apparatus for ELF magnetic fields. Bioelectromagnetics 25 : 582–591.

32. Volland H (1995) Handbook of Atmospheric Electrodynamics, Volume 1. CRC Press.

33. DolezelovaE, DolezelD, HallJC (2007) Rhythm defects caused by newly engineered null mutations in Drosophila's cryptochrome gene. Genetics 177 : 329–345.

34. DodsonCa, HorePJ, WallaceMI (2013) A radical sense of direction: signalling and mechanism in cryptochrome magnetoreception. Trends Biochem Sci 38 : 435–446.

35. OzturkN, SelbyC, AnnayevY, ZhongD, SancarA (2011) Reaction mechanism of Drosophila cryptochrome. Proc Natl Acad Sci U S A 108 : 516–521.

36. MaywoodES, CheshamJE, O'BrienJA, HastingsMH (2011) A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci U S A 108 : 14306–14311.

37. BerndtA, KottkeT, BreitkreuzH, DvorskyR, HennigS, et al. (2007) A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome. J Biol Chem 282 : 13011–13021.

38. PhillipsJB, JorgePE, MuheimR (2010) Light-dependent magnetic compass orientation in amphibians and insects: candidate receptors and candidate molecular mechanisms. J R Soc Interface 7 Suppl 2: S241–56.

39. NießnerC, DenzauS, StapputK, AhmadM, PeichlL, et al. (2013) Magnetoreception: activated cryptochrome 1a concurs with magnetic orientation in birds. J R Soc Interface 10 : 20130638.

40. PeschelN, ChenKF, SzaboG, StanewskyR (2009) Light-Dependent Interactions between the Drosophila Circadian Clock Factors Cryptochrome, Jetlag, and Timeless. Curr Biol 19 : 241–247.

41. OzturkN, VanVickle-ChavezSJ, AkileswaranL, Van GelderRN, SancarA (2013) Ramshackle (Brwd3) promotes light-induced ubiquitylation of Drosophila Cryptochrome by DDB1-CUL4-ROC1 E3 ligase complex. Proc Natl Acad Sci U S A 110 : 4980–4985.

42. CzarnaA, BerndtA, SinghHR, GrudzieckiA, LadurnerAG, et al. (2013) Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function. Cell 153 : 1394–1405.

43. VaidyaAT, TopD, ManahanCC, TokudaJM, ZhangS, et al. (2013) Flavin reduction activates Drosophila cryptochrome. Proc Natl Acad Sci U S A 110 : 20455–20460.

44. ZoltowskiBD, VaidyaAT, TopD, WidomJ, YoungMW, et al. (2011) Structure of full-length Drosophila cryptochrome. Nature 480 : 396–399.

45. LevyC, ZoltowskiBD, JonesAR, VaidyaAT, TopD, et al. (2013) Updated structure of Drosophila cryptochrome. Nature 495: E3–4.

46. OzturkN, SelbyCCP, ZhongD, SancarA (2013) Mechanism of Photosignaling by Drosophila Cryptochrome: Role of the Redox Status of the Flavin Chromophore. J Biol Chem 289 : 4634–4642.

47. OztürkN, SongS-H, SelbyCP, SancarA (2008) Animal type 1 cryptochromes. Analysis of the redox state of the flavin cofactor by site-directed mutagenesis. J Biol Chem 283 : 3256–3263.

48. BiskupT, PaulusB, OkafujiA, HitomiK, GetzoffED, et al. (2013) Variable electron transfer pathways in an amphibian cryptochrome: tryptophan versus tyrosine-based radical pairs. J Biol Chem 288 : 9249–9260.

49. BogdanovAM, MishinAS, Yampolsky IV, Belousov VV, ChudakovDM, et al. (2009) Green fluorescent proteins are light-induced electron donors. Nat Chem Biol 5 : 459–461.

50. FogleKJ, ParsonKG, Dahm Na, HolmesTC (2011) CRYPTOCHROME is a blue-light sensor that regulates neuronal firing rate. Science 331 : 1409–1413.

51. FosterRG, HankinsMW (2007) Circadian vision. Curr Biol 17: R746–51.

52. RosatoE, KyriacouCP (2006) Analysis of locomotor activity rhythms in Drosophila. Nat Protoc 1 : 559–568.

53. KirschvinkJL (1992) Uniform magnetic fields and double-wrapped coil systems. Bioelectromagnetics 13 : 401–411.

54. HastingsMH, ReddyAB, McMahonDG, MaywoodES (2005) Analysis of circadian mechanisms in the suprachiasmatic nucleus by transgenesis and biolistic transfection. Methods Enzymol 393 : 579–592.

55. AllebrandtKV, AminN, Müller-MyhsokB, EskoT, Teder-LavingM, et al. (2013) A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila. Mol Psychiatry 18 : 122–132.