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

Vanderstraeten, Jacques; Gailly, Philippe; Malkemper, E. Pascal

doi:10.1007/s00018-020-03463-5

Cited by 10 publications

(9 citation statements)

References 64 publications

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“…In this context, we also must mention that it is currently not yet clear whether all MCRYs are light-insensitive. At least a recent study indicates a possible light sensitivity of the mammalian MCRY2 [ 160 ]. Therefore, the possibility that DCRY is derived from a MCRY that was still light-sensitive but already active in the circadian clock cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

Deppisch

Helfrich‐Förster

Senthilan

2022

Genes

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The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. In this study, we took advantage of the large number of already sequenced and annotated genes available in databases and systematically searched for the protein sequences of CRY/PL family members in all taxonomic groups primarily focusing on metazoans and limiting the number of species per taxonomic order to five. Using BLASTP searches and subsequent phylogenetic tree and motif analyses, we identified five distinct photolyases (CPDI, CPDII, CPDIII, 6-4 photolyase, and the plant photolyase PPL) and six cryptochrome subfamilies (DASH-CRY, mammalian-type MCRY, Drosophila-type DCRY, cnidarian-specific ACRY, plant-specific PCRY, and the putative magnetoreceptor CRY4. Manually assigning the CRY/PL subfamilies to the species studied, we have noted that over evolutionary history, an initial increase of various CRY/PL subfamilies was followed by a decrease and specialization. Thus, in more primitive organisms (e.g., bacteria, archaea, simple eukaryotes, and in basal metazoans), we find relatively few CRY/PL members. As species become more evolved (e.g., cnidarians, mollusks, echinoderms, etc.), the CRY/PL repertoire also increases, whereas it appears to decrease again in more recent organisms (humans, fruit flies, etc.). Moreover, our study indicates that all cryptochromes, although largely active in the circadian clock, arose independently from different photolyases, explaining their different modes of action.

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Section: Discussionmentioning

confidence: 99%

The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

Deppisch

Helfrich‐Förster

Senthilan

2022

Genes

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“…The influence of magnetic fields from various sources on living cells, tissues, and organisms has gained increasing interest during recent years, beyond the research on geomagnetic compass orientation of migrating animals. Related studies focused on eventual harmful effects of human electromagnetic exposition in modern everyday life (Juutilainen et al 2018;Kaszuba-Zwoinska et al 2015;Vanderstraeten et al 2012Vanderstraeten et al , 2015World Health Organization 2007), as well as on the biological effects of electromagnetic radiation as future evidence based therapeutic tools (Cook et al 2015;Kiss et al 2015;Markov 2015;Morris and Skalak 2008;Rose et al 2016;Vadala et al 2016). In a previous study, we tested the impact of tNMR on the circadian clock and hypoxic signaling in zebrafish (Oliva et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In unsynchronized mouse fibroblasts, tNMR does not induce expression of rhythmicity. Vanderstraeten et al 2020). In humans, both isoforms were demonstrated to respond to changes in the external magnetic field when introduced into Drosophila cryptochrome-deficient strains (Foley et al 2011;Sherrard et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Several groups have been investigating the impact of low intensity electromagnetic fields (EMFs) on biological systems, as potential therapeutic tools (Carter et al 2020;Cook et al 2015;Kiss et al 2015;Markov 2015;Morris and Skalak 2008;Rose et al 2016;Vadala et al 2016) or as possible environmental hazards (Juutilainen et al 2018;Kaszuba-Zwoinska et al 2015;Vanderstraeten et al 2012Vanderstraeten et al , 2015World Health Organization 2007). Special interest was thereby given to the influence of low-intensity EMFs on circadian clocks, and here, in particular, on the flavoprotein family of Cryptochromes (Crys).…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Nuclear Magnetic Resonance affects the core clock mechanism and associated Hypoxia-inducible factor-1

Thöni

Oliva

Mauracher

et al. 2021

Chronobiology International

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The influence of low intensity electromagnetic fields on circadian clocks of cells and tissues has gained increasing scientific interest, either as a therapeutic tool or as a potential environmental hazard. Nuclear Magnetic Resonance (NMR) refers to the property of certain atomic nuclei to absorb the energy of radio waves under a corresponding magnetic field. NMR forms the basis for Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and, in a low-intensity form, for NMR therapy (tNMR). Since the circadian clock is bi-directionally intertwined with hypoxic signaling in vertebrates and mammals, we hypothesized that low intensity electromagnetic fields, such as tNMR, might not only affect circadian clocks but also Hypoxia-Inducible Factor-1α (HIF-1α). As master regulator of the hypoxic signaling pathway, HIF-1α is known to dampen the circadian amplitude under reduced oxygen availability, while the hypoxic response of cells and organisms, itself, is tightly clock controlled. In a first experiment, we investigated if tNMR is able to act as Zeitgeber for the core clock mechanism of unsynchronized zebrafish and mouse fibroblast cells, using direct light irradiation and treatment with the glucocorticoid Dexamethasone as references. tNMR significantly affected the cell autonomous clocks of unsynchronized mouse fibroblast cells NIH3-T3, but did not act as a Zeitgeber. Similar to light irradiation and in contrast to treatment with Dexamethasone, tNMR did not synchronize expression profiles of murine clock genes. However, irradiation with tNMR as well as light significantly altered mRNA and protein expression levels of Cryptochrome1, Cryptochrome2 and Clock1 for more than 24 h. Changes in mRNA and protein after different treatment durations, namely 6 and 12 h, appeared to be nonlinear. A nonlinear doseresponse relationship is known as hallmark of electromagnetic field induced effects on biological systems. The most prominent alterations were detected in murine HIF-1α protein, again in a nonlinear dose-response. In contrast to murine cells, zebrafish fibroblasts did not respond to tNMR at all. Light, a potent Zeitgeber for the peripheral clocks of fish, led to the expected synchronized clock gene oscillations of high amplitude, as did Dexamethasone. Hence, we conclude, mammalian peripheral clocks are more susceptible to tNMR than the direct light entrainable fish fibroblasts. Although light and tNMR did not act as Zeitgebers for the circadian clocks of unsynchronized murine cells, the significant observed effects might indicate downstream cellphysiological ramifications, which are worth future investigation. However, beside the effects tNMR exerts on the core clock mechanism of mammalian cells, the technology might be the first non-pharmacological approach to modify HIF-1α protein in cells and tissues. HIF-1α and the associated circadian clock play key roles in diseases with underlying ischemic background, such as infarct, stroke, and cancer and, also infectious diseases, such as Covid-19. Hence, low intensity magnet...

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“…Interestingly, while cryptochromes play a role in light entrainment in flies, in mammals, it functions as the critical repressive component of the TTFL. Recent studies suggest that the FAD pocket of mammalian CRY2, but not CRY1, retains some function and possibly works in a light-dependent manner ( 29 ). A mutation in the CRY2 FAD binding domain, p.A260T, was segregated with familial advanced sleep-wake phase disorder.…”

Section: Discussionmentioning

confidence: 99%

duperis a null mutation of Cryptochrome 1 in Syrian hamsters

Lee

Cal-Kayitmazbatir

Francey

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance We successfully identified the duper allele as a null mutation of Cryptochrome 1 in Syrian hamsters. Here, we have shown the use of fast homozygosity mapping as an effective approach to identify causal mutations in mammals, despite lacking chromosomal genome information. In the course of this work, we improved the draft Syrian hamster genome and generated datasets necessary to exploit Syrian hamsters as a modern genetic research model. The unique physiological features of Syrian hamsters make them a desirable model to investigate human diseases, including circadian disorders, cancer, heart function, metabolism, and infectious diseases (e.g., severe acute respiratory syndrome coronavirus 2).

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

Cited by 10 publications

References 64 publications

The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

Therapeutic Nuclear Magnetic Resonance affects the core clock mechanism and associated Hypoxia-inducible factor-1

duperis a null mutation of Cryptochrome 1 in Syrian hamsters

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