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Double-Cone Localization and Seasonal Expression Pattern Suggest a Role in Magnetoreception for European Robin Cryptochrome 4
Open accessAbstract
Birds seem to use a light-dependent, radical-pair-based magnetic compass. In vertebrates, cryptochromes are the only class of proteins that form radical pairs upon photo-excitation. Therefore, they are currently the only candidate proteins for light-dependent magnetoreception. Cryptochrome 4 (Cry4) is particularly interesting because it has only been found in vertebrates that use a magnetic compass. However, its structure and localization within the retina has remained unknown. Here, we sequenced night-migratory European robin (Erithacus rubecula) Cry4 from the retina and predicted the currently unresolved structure of the erCry4 protein, which suggests that erCry4 should bind Flavin. We also found that Cry1a, Cry1b, and Cry2 mRNA display robust circadian oscillation patterns, whereas Cry4 shows only a weak circadian oscillation. When we compared the relative mRNA expression levels of the cryptochromes during the spring and autumn migratory seasons relative to the non-migratory seasons in European robins and domestic chickens (Gallus gallus), the Cry4 mRNA expression level in European robin retinae, but not in chicken retinae, is significantly higher during the migratory season compared to the non-migratory seasons. Cry4 protein is specifically expressed in the outer segments of the double cones and long-wavelength single cones in European robins and chickens. A localization of Cry4 in double cones seems to be ideal for light-dependent magnetoreception. Considering all of the data presented here, especially including its localization within the European robin retina, its likely binding of Flavin, and its increased expression during the migratory season in the migratory bird but not in chicken, Cry4 could be the magnetoreceptive protein.
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“The double-cone localization of Cry4 as well as the fact that it is upregulated during the migration periods of migratory birds but not in chickens, is further confirmation that the molecule is viable as a magnetoreceptor [106].”
From The future of quantum biology (2018) · cites this paper as [106]
In the citing paper
“More recently, two studies have offered strong evidence for one of these four cryptochromes, Cry4, playing a role in the avian compass.”
From The future of quantum biology (2018) · cites this paper as [106]
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Hanić, M., Antill, L. M., Gehrckens, A. S., Schmidt, J., Görtemaker, K., Bartölke, R., El‐Baba, T. J., Xu, J., Koch, K., Mouritsen, H., et al. (2023) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c01305 · Cited by 10
Self-citationSensitivity enhancement of radical-pair magnetoreceptors as a result of spin decoherence
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Zhang, Y., Zeng, L., Wei, Y., Zhang, M., Pan, W., Sword, G. A., Yang, F., Chen, F., & Wan, G. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.954228 · Cited by 9
Rotov, A. Y., Goriachenkov, A. A., Cherbunin, R. V., Firsov, M. L., Chernetsov, N., & Astakhova, L. A. (2022) · Cells · doi:10.3390/cells11193056 · Cited by 10
Long-Time Oxygen and Superoxide Localization in Arabidopsis thaliana Cryptochrome
Salerno, K. M., Domenico, J., Le, N. Q., Balakrishnan, K., McQuillen, R. J., Stiles, C. D., Solov’yov, I. A., & Martino, C. F. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00325 · Cited by 11
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Self-citationHolub, D., Kubař, T., Mast, T., Elstner, M., & Gillet, N. (2019) · Physical Chemistry Chemical Physics · doi:10.1039/c9cp00694j · Cited by 10
Quantum mechanical spin dynamics of a molecular magnetoreceptor
Lindoy, L. P., Fay, T. P., & Manolopoulos, D. E. (2020) · The Journal of Chemical Physics · doi:10.1063/5.0006411 · Cited by 11
Introducing P ep McConst —A user‐friendly peptide modeler for biophysical applications
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Self-citationImmunohistochemical characterization of bipolar cells in four distantly related avian species
Balaji, V., Haverkamp, S., Seth, P. K., Günther, A., Mendoza, E., Schmidt, J., Herrmann, M., Pfeiffer, L. L., Němec, P., Scharff, C., et al. (2022) · The Journal of Comparative Neurology · doi:10.1002/cne.25443 · Cited by 10
Self-citationYee, C., Bartölke, R., Görtemaker, K., Schmidt, J., Leberecht, B., Mouritsen, H., & Koch, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-79699-z · Cited by 9
Self-citationElectroretinographic study of the magnetic compass in European robins
Astakhova, L. A., Rotov, A. Y., Cherbunin, R. V., Goriachenkov, A. A., Kavokin, K. V., Firsov, M. L., & Chernetsov, N. (2020) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2020.2507 · Cited by 9
The secrets of cryptochromes: photoreceptors, clock proteins, and magnetic sensors
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Self-citationA hybrid compass mechanism combining radical pairs and magnetite crystals
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Magnetoreception in the Retina of the Domestic Pigeon Columbia livia: a Retinographic Search
Rotov, A. Y., Cherbunin, R. V., Kavokin, K. V., Chernetsov, N., Firsov, M. L., & Astakhova, L. A. (2018) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s00220930180600121 · Cited by 8
Metadata
- Authors
- Günther, A., Einwich, A., Sjulstok, E., Feederle, R., Bolte, P., Koch, K.-W., Solov’yov, I. A., & Mouritsen, H.
- Affiliations
- Carl von Ossietzky Universität Oldenburg (DE)
- University of Southern Denmark (DK)
- Helmholtz Munich (DE)
- Corresponding author
- Mouritsen, Henrik
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 28
- Issue
- 2
- Pages
- 211-223.e4
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2781607775
- Cited by
- 204
- References
- 82
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 12 · 2023: 27 · 2022: 22 · 2021: 32 · 2020: 23 · 2019: 27 · 2018: 14
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- DFG (FOR701, MO 1408/1-2)
- GRK (1885)
- Volkswagen Stiftung
- Air Force Office of Scientific Research (FA9550-14-1-0095)
- Lundbeck Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Physical Sciences › Earth and Planetary Sciences › Geophysics › Geomagnetism and Paleomagnetism Studies
- Keywords
- magnetoreception, European robin, Erithacus rubecula, retina, circadian gene expression, seasonal gene expression, bird migration, radical pair mechanism, flavin binding, photoreceptor outer segments
- MeSH terms
- Animals, Chickens, Gene Expression Regulation, Perception, Seasons, Sequence Analysis, DNA, Retinal Cone Photoreceptor Cells, Songbirds, Animal Migration, Avian Proteins, Cryptochromes, Magnetic Fields
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