Cryptochrome Blue Light Photoreceptors Are Activated through Interconversion of Flavin Redox States

Bouly, Jean-Pierre; Schleicher, Erik; Dionisio-Sese, Maribel L.; Vandenbussche, Filip; Straeten, Dominique Van Der; Bakrim, Nadia; Meier, Stefan; Batschauer, Alfred; Galland, Paul; Bittl, Robert; Ahmad, Margaret

doi:10.1074/jbc.m609842200

Cited by 384 publications

(532 citation statements)

References 49 publications

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“…k D >> k F and hence E >> 1). It has been suggested that the signalling state of the putative cryptochrome magnetosensor contains FAD that is either singly reduced (FAD  or FADH  ) 61 or, after further photoexcitation, fully reduced (FADH  ) 12,13 . Either way, rapid reduction of the donor-radical would stabilise the signalling state against reverse electron transfer so promoting signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Chemical amplification of magnetic field effects relevant to avian magnetoreception

et al. 2016

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Magnetic fields as weak as the Earth's can change the yields of radical pair reactions even though the energies involved are orders of magnitude smaller than k B T at room temperature. Proposed as the source of the light-dependent magnetic compass in migratory birds, the radical pair mechanism is thought to operate in cryptochrome flavoproteins in the retina. Here we demonstrate that the primary magnetic field effect on flavin photoreactions can be chemically amplified by slow radical termination reactions under conditions of continuous photoexcitation. The nature and origin of the amplification are revealed by studies of the intermolecular flavin-tryptophan and flavin-ascorbic acid photocycles and the closely related intramolecular flavin-tryptophan radical pair in cryptochrome. Amplification factors of up to 5.6 have been observed for magnetic fields weaker than 1 mT. Substantial chemical amplification could have a significant impact on the viability of a cryptochrome-based magnetic compass sensor.2 Amongst other directional cues, migratory birds use a light-dependent geomagnetic compass for orientation and navigation [1][2][3] . Although the primary detection mechanism is unclear, the evidence currently points to magnetically sensitive photochemical reactions in cryptochrome proteins located in the retina [4][5][6] . Cryptochromes 7 contain the chromophore flavin adenine dinucleotide (FAD), photoexcitation of which can trigger three consecutive intra-protein electron transfers along a conserved triad of tryptophan (Trp) residues to produce a (FAD  Trp  ) radical pair [8][9][10] . This form of cryptochrome is magnetically sensitive in vitro and possibly also in vivo [11][12][13] . Similar magnetosensitivity is conceivable in other cryptochrome-derived radical pairs in which FAD  or its protonated form, FADH  , is paired with an ascorbic acid radical 14 or, less plausibly, superoxide, 2 O ·- 15,16 . There appear to be different electron transfer pathways in some cryptochromes 17,18 , but no evidence so far that they give rise to magnetic field effects.The radical pair mechanism is well established as the source of magnetic field effects on chemical reactions 19 . Remarkably, the magnetic interactions of electron spins in organic radicals can result in significant changes in reaction kinetics and product yields even though those interactions are many orders of magnitude weaker than the thermal energy, k B T. The sensitivity to applied magnetic fields derives from the coherent spin dynamics of pairs of radicals formed in spincorrelated states. Several conditions need to be satisfied for a radical pair to be suitable as a geomagnetic compass sensor 5 : (a) the electron spin in at least one of the radicals must interact anisotropically with nuclear spins; (b) the mutual interaction of the two electron spins should be small; (c) the radical pair must react spin-selectively; (d) its lifetime should not be too short; and (e) the electron spin relaxation must be relatively slow. Studies of isolated cry...

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Section: Discussionmentioning

confidence: 99%

Chemical amplification of magnetic field effects relevant to avian magnetoreception

et al. 2016

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“…3 Polyclonal antibody used for cry2 detection has been raised to the C-terminal domain as used previously. 6 …”

Section: Disclosure Of Potential Conflicts Of Interestmentioning

confidence: 99%

Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role

Jourdan

Martino

El‐Esawi

et al. 2015

Plant Signaling & Behavior

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Cryptochromes are blue-light absorbing flavoproteins with many important signaling roles in plants, including in deetiolation, development, and stress response. They interact with downstream signaling partners such as transcription factors and components of the proteasome, and thereby alter regulation of nuclear gene expression in a light dependent manner. In a prior study, it has also been shown that Arabidopsis cry1 activation by blue light results in direct enzymatic conversion of molecular oxygen (O2) to ROS (reactive oxygen species) in vivo leading to cell death in overexpressing lines. Here we extend these observations to show that Atcry2 is translocated from the cytosol to the nucleus in response to blue light illumination, resulting in nuclear accumulation of ROS in expressing insect cell cultures. These observations suggest that ROS formation may represent a novel means of signaling by Atcry2 distinct from, and perhaps complementary to, the currently known mechanism of light-mediated conformational change.

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“…In contrast, as will be discussed below, some studies have suggested that photoinduced electron 126 ÖZTÜRK ET AL. transfer is the key photophysical event in the CRY photocycle (Zeugner et al 2005;Banerjee et al 2007;Bouly et al 2007). …”

Section: The "Trp Triad" and Photoreductionmentioning

confidence: 99%

“…Most of these studies have been done on Arabidopsis CRYs. First, it has been reported that AtCRY1 and AtCRY2 made in insect cells contain flavin in the FAD ox state and that exposure of the insect cells expressing the CRYs to blue light reduces the FAD ox to a FADH°neutral radical (Banerjee et al 2007;Bouly et al 2007). This was complemented by in vitro experiments that demonstrated that exposure of AtCRYs to light followed by a dark phase under aerobic conditions cause the following transitions:…”

Section: Functional Properties Of Animal Cryptochrome Cryptochrome Phmentioning

confidence: 99%

Structure and Function of Animal Cryptochromes

Öztürk

Song²,

Özgür³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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Cryptochrome (CRY) is a photolyase-like flavoprotein with no DNA-repair activity but with known or presumed blue-light receptor function. Animal CRYs have DNA-binding and autokinase activities, and their flavin cofactor is reduced by photoinduced electron transfer. In Drosophila, CRY is a major circadian photoreceptor, and in mammals, the two CRY proteins are core components of the molecular clock and potential circadian photoreceptors. In mammals, CRYs participate in cell cycle regulation and the cellular response to DNA damage by controlling the expression of some cell cycle genes and by directly interacting with checkpoint proteins. in response to blue light (Koornneef et al. 1980), was isolated and sequenced, it revealed high sequence homology with Escherichia coli photolyase, and hence, it was in retrospect, correctly speculated that HY4 encoded a blue light photoreceptor and not a signal transducer involved in blue light response (Ahmad and Cashmore 1993). Later, this protein was named cryptochrome 1 (Lin et al. 1995, and a second Arabidopsis protein that has high homology with CRY1 identified by genomics was named CRY2 . The role of CRY in Arabidopsis growth (CRY1) and differentiation (CRY2) was well established by 1995 (see Guo et al. 1998). However, as late as 1997, it was thought that CRY had no role in circadian photoreception in plants (Millar and Kay 1997).The first report implicating CRY in the circadian clock of any organism, plant or animal, came about from the study of DNA repair, in particular, the repair of UV damage in humans by photolyase. This issue had been controversial for nearly 25 years when Li et al. (1993) conducted an exhaustive study with a highly specific and sensitive assay, concluding that humans, like all placental mammals, lacked photolyase (Li et al. 1993). However, a 1995 release of a human expressed sequence tag (EST) list contained a "photolyase ortholog" entry (Adams et al. 1995). In light of this finding and the discovery of a photolyase in Drosophila and rattlesnake (Todo et al. 1993Kim et al. 1996) that repairs the minor UV-induced lesion, the (6-4) photoproduct, in contrast to the classic photolyase that repairs cyclobutane pyrimidine dimers (CPDs), the earlier conclusion regarding the lack of photolyase in humans needed reevaluation. This was done by Hsu et al. (1996) who, in addition to the "photolyase ortholog" in public databases, discovered a second human photolyase gene. Human cells expressing both genes and recombinant proteins encoded by both genes were tested for CPD and (6-4) photolyase activities and were found to lack both. Moreover, the proteins encoded by these genes, like most photolyases (Johnson et al. 1988) and Arabidopsis CRY (Lin et al. 1995; Malhorta et al. 1995), contained FAD (flavin-adenine dinucleotide) and a pterin cofactor. Therefore, it was concluded that these proteins were not repair enzymes but that, like Arabidopsis CRYs, they performed non-repair-related blue light functions and were named human CRY1 and 2 (Hsu et al. 1996). In humans ...

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Cryptochrome Blue Light Photoreceptors Are Activated through Interconversion of Flavin Redox States

Cited by 384 publications

References 49 publications

Chemical amplification of magnetic field effects relevant to avian magnetoreception

Chemical amplification of magnetic field effects relevant to avian magnetoreception

Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role

Structure and Function of Animal Cryptochromes

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