Double-Cone Localization and Seasonal Expression Pattern Suggest a Role in Magnetoreception for European Robin Cryptochrome 4

Curr Biol. 2018 Jan 22;28(2):211-223.e4. doi: 10.1016/j.cub.2017.12.003. Epub 2018 Jan 4.


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.

Keywords: bird migration; eye; magnetic sense; magnetic sensing; magneto-perception; navigation; orientation; photoreceptor; photoreceptor cells; vision.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Migration / radiation effects*
  • Animals
  • Avian Proteins / genetics*
  • Avian Proteins / metabolism
  • Chickens / genetics
  • Chickens / physiology
  • Cryptochromes / genetics*
  • Cryptochromes / metabolism
  • Gene Expression Regulation / radiation effects*
  • Magnetic Fields*
  • Perception
  • Retinal Cone Photoreceptor Cells / radiation effects*
  • Seasons
  • Sequence Analysis, DNA
  • Songbirds / genetics
  • Songbirds / physiology*


  • Avian Proteins
  • Cryptochromes