Cryptochrome Sunlight is the ultimate energy source for nearly all life on Earth.

Yet, its importance to life extends far beyond a source of energy because it is also a critical information carrier. Plants and animals sample the light environment to gain information about local surroundings, time of day, and season of the year. Although animals can use opsin-based visual systems to capture information from their light environments, plants don't have eyes in a metazoan sense. The ability of plants to respond to light is achieved through a number of photoreceptor families, which include red and far-red light sensing phytochromes (PHY) and blue-light specific phototropins and cryptochromes (CRY). Cryptochromes are flavoproteins that share structural similarity to DNA photolyases but lack photolyase activity. All members of the cry/photolyase family share an amino-terminal photolyase-related (PHR) domain that is responsible for chromophore binding (both a primary/catalytic flavin and a second light-harvesting deazaflavin or pterin) and lightabsorbing capacity. Another difference between crys and photolyases is the presence of a carboxyl-terminal extension beyond the PHR domain in the crys that is absent in the photolyases.

( Blue Light Signaling through the Cryptochromes and Phototropins. So That's What the Blues Is All About) Found in plants and animals and even some bacteria Photoreceptors regulate entrainment of light of the circadian clock in plants and animals Probably evolutionary descendants DNA photolyases DNA repair enzymes that repair damage caused by exposure to UV light. The mechanism requires visible light, preferably from the violet/blue end of the spectrum 3 groups animal cryptochromes (CRY1), plant cryptochromes (CRY2) and CRYDASH proteins with the exception of CRY-DASH (or CRY3), cryptochromes are composed of two domains, an amino-terminal photolyase-related (PHR) region and a carboxy-terminal domain (DAS) of varying size. The PHR region appears to bind two chromophores; one chromophore is flavin adenine dinucleotide (FAD) and the other 5,10methenyltetrahydrofolate (pterin or MTHF)

circadian clock - The circadian clock is the molecular oscillator that drives various overt circadian rhythms in most organisms, allowing the organisms to anticipate and adapt to the environmental changes dominated by the daily 24-hour light/dark cycle as well as the annual photoperiod cycle on earth (Devlin and Kay, 2001; Harmer, 2009). Light is the most dominant environmental cue that enables the circadian clock and physiological activities of an organism to be synchronized to the daily cycles of environmental changes (Devlin and Kay, 2001; Cashmore, 2003; Sancar, 2003). Cryptochrome as a major photoreceptor or intrinsic component of the circadian clock was demonstrated in 1998 in Arabidopsis, Drosophila, and mouse (Emery et al., 1998; Somers et al., 1998; Stanewsky et al., 1998; Thresher et al., 1998).

Animals Cryptochromes are a central circadian oscillator In Drosophila, cryptochrome (dCRY) acts as a blue-light photoreceptor that directly modulates light input into the circadian clock[22], while in mammals, cryptochromes (CRY1 and CRY2) act astranscription repressors within the circadian clockwork.[23] Some insects, including the monarch butterfly, have both a mammallike and a Drosophila-like version of cryptochrome, providing evidence for an ancestral clock mechanism involving both light sensing and transcriptional repression roles for cryptochrome. -mammal - Cryptochrome is one of the four groups of mammalian clock genes/proteins that generate a transcription-translation negative-feedback loop (TTFL), along with Period (PER), CLOCK, and BMAL1.[32] In this loop, CLOCK and BMAL1 proteins are transcriptional activators, which together bind to the promoters of the Cry and Per genes and activate their transcription.[32] The CRY and PER proteins then bind to each other, enter the nucleus, and inhibit CLOCKBMAL1 activated transcription. Insect- insect CRY1 is photosensitive, whereas photo-insensitive CRY2 functions to potently inhibit clock-relevant CLOCK:CYCLE-mediated transcription. Magnetorecpetion wide variety of living organisms have the ability to perceive magnetic fields and can use information from the earth's magnetic field in orientation behavior. salmon (Oncorhynchus nerka), sea turtles (Dermochelys coriacea), spotted newts (Notophthalmus viridescens), lobsters(Panulirus argus), honeybees (Apis mellifera), and fruitflies (Drosophila melongaster) can all perceive and utilize geomagnetic field information. Migratory birds (e.g. European robins (Erithacus rubecula), silvereyes (Zosterops l. lateralis), garden warblers (Sylvia borin)), who use the earth's magnetic field. Human CRY2 has the molecular capapbility of function as a light-sensitive magnetooreceptor. (Human cryptochrome exhibits light-dependent magnetosensitivity) .

Plants Cryptochromes act as receptors controlling photomorphogenesis in response to blue or ultraviolet light Arabidopsis cryptochromes work together with the red/far-red light receptor phytochromes to regulate various light responses, including the regulation of cell

elongation and photoperiodic flowering, and are also found to act together with the blue light receptor phototropins to mediate blue light regulation of stomatal opening. mediate phototropism, or directional growth towards a light source, in response to blue light. This response is now known to have its own set of photoreceptors, the phototropins. Unlike phytochromes and phototropins, cryptochromes are not kinases. Their flavin chromophore is reduced by light and transported into thecell nucleus, where it affects the turgor pressure and causes subsequent stem elongation. Specifically, Cry2 is responsible for blue-light mediated cotyledon and leaf expansion. Cry2 overexpression in transgenic plants increases blue light-stimulated cotyledon expansion, which results in many broad leaves and no flowers, rather than a few primary leaves with a flower .( The Cryptochrome Blue Light Receptors) De-etiolation is the major developmental switch of young seedlings emerging from the darkness under soil and becoming exposed to light. De-etiolation is characterized by several morphological changes, including hypocotyl growth arrest, cotyledon expansion, and chloroplast development. Light inhibits hypocotyl elongation, but stimulates cotyledon expansion and conversion of etioplasts to chloroplasts (Nemhauser and Chory, 2002) phytochromes and cryptochromes both mediate blue light stimulation of de-etiolation in Arabidopsis (Figure 1B), and their functions in deetiolation are dependent on both transcriptional and post-transcriptional regulation of gene expression (Chen et al., 2004; Jiao et al., 2007). many genes, such as COP1, SPA1, HY5/HYH, HFR1, PP7, SUB1, SHB1, BIT1, OBP3, HRB1, and ATAB2 have been found to participate in cryptochrome regulation of de-etiolation In contrast to the inhibitory effect of cryptochromes on cell elongation in hypocotyls, cryptochromes mediate blue-light stimulation of cell expansion in cotyledons (Feldman, 1984; Blum et al., 1994; Casal and Mazzella, 1998; Lin et al., 1998; Neff and Chory, 1998). Both CRY1 and CRY2 mediate blue-light stimulation of cotyledon expansion. A recent observation that the cry1cry2 double mutant displayed an increased drought tolerance has led to a finding that cryptochromes also contribute to the bluelight stimulation of stomata opening (Mao et al., 2005) (Figure 1D). It was found that the cry1cry2 mutant and CRY1-overexpressing plants exhibit a reduced or increased stomata opening in response to blue light, respectively. In addition to stimulating stomata opening, light also stimulates stomata development. Light stimulation of guard cell development is a complex process that includes initiation of asymmetric cell divisions, proliferation of precursor cells, and differentiation of stomatal guard cells that form stomata. It has been shown that blue, red, and far-red light all stimulate guard cell development (Bergmann and Sack, 2007; Kang et al., 2009). cry1 mutant plants are impaired in blue-light stimulation of stomata development (Kang et al., 2009). In addition to the light responses discussed above, cryptochromes may mediate light regulation of other aspects of plant growth and development. For example, cryptochromes in Arabidopsis and other plants have been shown to regulate plant height (Weiler et al., 2001; Giliberto et al., 2005;Platten et al., 2005), fruit and ovule development (El-Assal et al., 2004), seed dormancy (Goggin et al., 2008), apical dominance (Weller et al., 2001; Giliberto et al., 2005), the high-light stress response

(Kleine et al., 2007), osmotic stress response (Xu et al., 2009), cell cycle program of stem cells (Lopez-Juez et al., 2008), responses to bacterial and viral pathogens (Jeong et al., 2010; Wu and Yang, 2010), as well as magnetoreception, tropic growth, and programmed cell death (Figure 1). Unlike de-etiolation and floweringtime phenotype that are unambiguous and easy to observe, some minor phenotypes detected in the loss-of-function cryptochrome mutants are sometimes subtle, ambiguous, controversial, or undetectable unless being in a specific genetic background. Contrary to a conventional wisdom that light should inhibit root elongation (to prevent roots from growing out of the soil), it was reported that blue light stimulated root elongation and that CRY1 mediated this response (Canamero et al., 2006). In contrast, CRY2 appears to antagonize the function of CRY1 in regulating the root cell elongation. light-dependent PCD initiated by reactive oxygen species (ROS) resulting from impaired photosynthesis electron transport under stress conditions is unique to plants. It was found that the cry1 mutation suppresses blue light- and ROSdependent PCD in Arabidopsis. Cryptochromes and phytochromes may act together to modulate the functions of phototropins in many if not all of the phototropin-mediated blue light responses. For example, cryptochromes and phytochromes may act to enhance the phototropin action at lower fluence but antagonized the function of phototropin at high fluence analogous to the phytochrome-dependent red light suppression of gravitropism, CRY1 and CRY2 mediate bluelight suppression of gravitropism or blue light activation of random hypocotyl bending (Ohgishi et al., 2004). Light-dependent suppression of gravitropism is likely a consequence of photoreceptor-dependent regulation of the expression of genes involved in hormone metabolism, transport, or signaling. For example, cryptochromes mediate blue-light inhibition of the expression of the PGP19/ABSB9 gene. PGP19/ABSB9 encodes an ABC-type auxin transporter required for appropriate auxin transport and gravitropic growth. Used for detection of blue light for quantitative cues of water depth for heterophyllus plants

Phototrophin Phototropins are autophosphorylating protein kinases that activate in response to blue light. When blue light hits the phototropin protein in the cell membrane, the phototropin protein will unfold and undergo phosphorylation that can cause a cascade of events inside of the cell. Phototropins specifically will cause stems to bend towards light, andstomata to open. Also, phototropins are important in chloroplast movements inside the cell. They also mediate the first changes in stem elongation in blue light (before cryptochromes become active) and phototropin 1 also is required for blue light mediated transcript destabilization of specific mRNAs in the cell.

Fig. 1. Domain organization of the three classes of known plant photoreceptors and a typical prokaryotic photolyase. PhyA, Arabidopsis phytochrome A; Phy3, Adiantum capillusvenerisphy3; Phototropin, Arabidopsis phototropin (nph1); Cry1, Arabidopsis cry1. Chromophores: ph, phytochromobilin; FMN; FAD; d, deazaflavin; p, pterin.

http://www.plantcell.org/content/14/suppl_1/S207.full