Millitesla magnetic field effects on the photocycle of an animal cryptochrome

Sheppard, Dean M. W.; Li, Jing; Henbest, Kevin B.; Neil, Simon R. T.; Maeda, Kiminori; Storey, Jonathan G.; Schleicher, Erik; Biskup, Till; Rodriguez, Ryan; Weber, Stefan; Hore, P. J.; Timmel, Christiane R.; Mackenzie, Stuart R.

doi:10.1038/srep42228

Cited by 79 publications

(98 citation statements)

References 32 publications

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“…The spin states of these chemical intermediates, in turn, influence the rate of CRY activation, which is transduced into neuronal impulses through an as yet unknown pathway. Even though sensitivity to weak MF could hitherto only be demonstrated in the plant Arabidopsis thaliana [36] and fruit fly (Drosophila melanogaster) CRY [37], a wealth of evidence supports the involvement of CRY in the ability of birds to orient to the geomagnetic field [35]. From recent data, the magnetic sense in birds is based on a type IV CRY (CRY 4) localized in cones of the avian retina [38].…”

Section: Cryptochromes Of Mammalsmentioning

confidence: 99%

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Vanderstraeten

Gailly

Malkemper

2020

Cell. Mol. Life Sci.

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The mechanisms that synchronize the biorhythms of the mammalian retina with the light/dark cycle are independent of those synchronizing the rhythms in the central pacemaker, the suprachiasmatic nucleus. The identity of the photoreceptor(s) responsible for the light entrainment of the retina of mammals is still a matter of debate, and recent studies have reported contradictory results in this respect. Here, we suggest that cryptochromes (CRY), in particular CRY 2, are involved in that light entrainment. CRY are highly conserved proteins that are a key component of the cellular circadian clock machinery. In plants and insects, they are responsible for the light entrainment of these biorhythms, mediated by the light response of their flavin cofactor (FAD). In mammals, however, no light-dependent role is currently assumed for CRY in light-exposed tissues, including the retina. It has been reported that FAD influences the function of mammalian CRY 2 and that human CRY 2 responds to light in Drosophila, suggesting that mammalian CRY 2 keeps the ability to respond to light. Here, we hypothesize that CRY 2 plays a role in the light entrainment of retinal biorhythms, at least in diurnal mammals. Indeed, published data shows that the light intensity dependence and the wavelength sensitivity commonly reported for that light entrainment fits the light sensitivity and absorption spectrum of light-responsive CRY. We propose experiments to test our hypothesis and to further explore the still-pending question of the function of CRY 2 in the mammalian retina.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Cryptochromes Of Mammalsmentioning

confidence: 99%

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Vanderstraeten

Gailly

Malkemper

2020

Cell. Mol. Life Sci.

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“…Ritz, Adem and Schulten were the first to speculate that the underlying radical pair could be formed by photo-excitation in the animals' eyes in cryptochromes [11], a class of blue-light sensitive flavo-proteins that shares some similarity with photolyases [12]; this supposition still applies;. To date, cryptochromes are the only vertebrate proteins known to form radical pairs in a physiologically significant photoreaction and their relevancy to magnetoreception has indeed been implicated in a multitude of studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. The reader is referred to the many reviews on this subject for a more detailed exposition [10,27,29,30].…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

2018

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Birds appear to be equipped with a light-dependent, radical-pair-based magnetic compass that relies on truly quantum processes. While the identity of the sensory protein has remained speculative, cryptochrome 4 has recently been identified as the most auspicious candidate. Here, we report on allatom molecular dynamics (MD) simulations addressing the structural reorganisations that accompany the photoreduction of the flavin cofactor in the European robin cryptochrome 4 (ErCry4). Extensive MD simulations reveal that the photo-activation of ErCry4 induces large-scale conformational changes on short (hundreds of nanoseconds) timescales. Specifically, the photo-reduction is accompanied with the release of the C-terminal tail, structural rearrangements in the vicinity of the FAD-binding site, and the noteworthy formation of an α-helical segment at the N-terminal part. Some of these rearrangements appear to expose potential phosphorylation sites. We describe the conformational dynamics of the protein using a graph-based approach that is informed by the adjacency of residues and the correlation of their local motions. This approach reveals densely coupled reorganisation entities, i.e. graph communities, which could facilitate an efficient signal transduction due to a high density of hubs. These communities are interconnected by a small number of highly important residues. The network approach clearly identifies the sites restructuring upon photoactivation, which appear as protrusions or delicate bridges in the reorganisation network. We also find that, unlike in the homologous cryptochrome from D. melanogaster, the release of the C-terminal domain does not appear to be correlated with the transposition of a histidine residue close to the FAD cofactor.

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“…There is significant but largely circumstantial evidence in support of this hypothesis (4): the avian compass is known to be light dependent (7,8), a proof-of-principle model radical-pair compass has been demonstrated (9), and cryptochromes, the proposed receptor proteins (2), form magnetically sensitive radical pairs when excited in vitro with blue light (10,11). However, it is the disorientation of birds exposed to very weak radiofrequency magnetic fields (1,12) that arguably rules out the competing hypotheses based on superparamagnetic (13) or ferrimagnetic particles (14).…”

Section: Introductionmentioning

confidence: 99%

Disruption of Magnetic Compass Orientation in Migratory Birds by Radiofrequency Electromagnetic Fields

Hiscock

Mouritsen

Manolopoulos

et al. 2017

Biophysical Journal

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The radical-pair mechanism has been put forward as the basis of the magnetic compass sense of migratory birds. Some of the strongest supporting evidence has come from behavioral experiments in which birds exposed to weak time-dependent magnetic fields lose their ability to orient in the geomagnetic field. However, conflicting results and skepticism about the requirement for abnormally long quantum coherence lifetimes have cast a shroud of uncertainty over these potentially pivotal studies. Using a recently developed computational approach, we explore the effects of various radiofrequency magnetic fields on biologically plausible radicals within the theoretical framework of radical-pair magnetoreception. We conclude that the current model of radical-pair magnetoreception is unable to explain the findings of the reported behavioral experiments. Assuming that an unknown mechanism amplifies the predicted effects, we suggest experimental conditions that have the potential to distinguish convincingly between the two distinct families of radical pairs currently postulated as magnetic compass sensors. We end by making recommendations for experimental protocols that we hope will increase the chance that future experiments can be independently replicated.

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Millitesla magnetic field effects on the photocycle of an animal cryptochrome

Cited by 79 publications

References 32 publications

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

Disruption of Magnetic Compass Orientation in Migratory Birds by Radiofrequency Electromagnetic Fields

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