Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein

Cells. 2022 Jun 27;11(13):2043. doi: 10.3390/cells11132043.

Abstract

Background: Night-migratory birds sense the Earth's magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that the light-induced formation of a radical-pair in European robin cryptochrome 4a (ErCry4a) is the primary signaling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signaling involving the α-subunit of the cone-secific heterotrimeric G protein from European robin.

Methods: Protein-protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer.

Results: Surface plasmon resonance studies showed direct interaction, revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer.

Conclusions: Our results suggest that ErCry4a and the G protein also interact in living cells and might constitute the first biochemical signaling step in radical-pair-based magnetoreception.

Keywords: G protein α-subunit; cryptochrome; magnetoreception; protein-protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryptochromes* / metabolism
  • GTP-Binding Proteins / metabolism
  • Magnetic Fields
  • Retina / metabolism
  • Songbirds* / metabolism

Substances

  • Cryptochromes
  • GTP-Binding Proteins

Grants and funding

K.-W.K. and H.M. gratefully acknowledge funding from the DFG research training group grant GRK 1885, from the DFG SFB 1372 “Magnetoreception and navigation in vertebrates” and from an AFOSR grant (No. FA9550-14-1-0095). H.M. acknowledges funding from the European Research Council (under the European Union’s Horizon 2020 research and innovation programme, grant agreement no. 810002 (Synergy Grant: “QuantumBirds”). E.B. gratefully acknowledges funding from the DFG SFB 1372 “Magnetoreception and navigation in vertebrates”.