Cryptochrome Mediates Light-Dependent Magnetosensitivity of Drosophila's Circadian Clock

Abstract

Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY) has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 μT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cryb and cryOUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system for CRY-dependent magnetic sensitivity. Furthermore, given that CRY occurs in multiple tissues of Drosophila, including those potentially implicated in fly orientation, future studies may yield insights that could be applicable to the magnetic compass of migratory birds and even to potential magnetic field effects in humans.

Mechanism of Photosignaling by Drosophila Cryptochrome

“…Largely based on this fact, it was also proposed that electron transfer through the Trp triad is the primary photochemical event in dCRY signaling (25). Moreover, the electron transfer through the Trp triad to flavin generates a charge separated radical pair, and this has led to the proposal that dCRY acts not only as a circadian photoreceptor but also as a magnetoreceptor (23,24). In support of a magnetosensory function of dCRY, it was found that Drosophila was capable of sensing the magnetic field and that the magnetosensory function was lost in dCRY null mutants (23,24).…”

“…Moreover, the electron transfer through the Trp triad to flavin generates a charge separated radical pair, and this has led to the proposal that dCRY acts not only as a circadian photoreceptor but also as a magnetoreceptor (23,24). In support of a magnetosensory function of dCRY, it was found that Drosophila was capable of sensing the magnetic field and that the magnetosensory function was lost in dCRY null mutants (23,24). However, mutations in the Trp triad did not affect the magnetosensory capacity of the fly (23), raising some doubts about the role of electron transfer through the Trp triad in photosensory (circadian and magnetic) function of dCRY.…”

“…1A. The Trp triad has been implicated in CRY function ranging from plant growth in Arabidopsis to circadian photoreception in Drosophila (5) to magnetoreception in flies (23,24) and birds (2).…”

Influence of temperature on the infradian growth rhythm inUlva lactuca(Chlorophyta)

“…It is now established that electromagnetic fields, even if very weak, can have an influence on basic biological functions, such as circadian rhythmicity of Drosophila's locomotor activity (Yoshii et al, 2009), orientation and navigation in birds (Wiltschko & Wiltschko, 2005;Rodgers & Horea, 2009;Wu & Dickman 2012) and larval development of the Japanese newt, Cynops pyrrhogaster (Asashima et al, 1991). It is also known that electromagnetic shielding causes sharp phase shifts and amplitude changes of infradian rhythmicity of the pain sensitivity in land snails Helix albescens (Kostyuk & Temuryants, 2009) and of mobility in the planarian Dugesia tegrina (Yarmolyuk, 2010).…”

Light-activated Cryptochrome Reacts with Molecular Oxygen to Form a Flavin–Superoxide Radical Pair Consistent with Magnetoreception

“…Cryptochromes have lost the ability to repair DNA, but they play a key role in controlling the growth and development in plants and in the circadian clock in plants and animals (4). Furthermore, recent evidence suggests that cryptochromes are likely to function as light-dependent magnetic field sensors, used for example by insects or migratory birds and fish for directional responses (5)(6)(7).…”