The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor

Abstract

The biophysical and molecular mechanisms that enable animals to detect magnetic fields are unknown. It has been proposed that birds have a light-dependent magnetic compass that relies on the formation of radical pairs within cryptochrome molecules. Using spectroscopic methods, we show that pigeon cryptochrome clCRY4 is photoreduced efficiently and forms long-lived spin-correlated radical pairs via a tetrad of tryptophan residues. We report that clCRY4 is broadly and stably expressed within the retina but enriched at synapses in the outer plexiform layer in a repetitive manner. A proteomic survey for retinal-specific clCRY4 interactors identified molecules that are involved in receptor signaling, including glutamate receptor–interacting protein 2, which colocalizes with clCRY4. Our data support a model whereby clCRY4 acts as an ultraviolet-blue photoreceptor and/or a light-dependent magnetosensor by modulating glutamatergic synapses between horizontal cells and cones.

The Magnetic Compass of Birds: The Role of Cryptochrome

“…Based on studies with purified Cry1, Kutta et al (2017) questioned whether vertebrate Cry1 indeed had FAD bound and hence could be photo-reduced (see also Hochstoeger et al, 2020 ), although Liedvogel et al (2007) reported that avian Cry 1a contained FAD and could absorb blue light. An in vivo study also showed that at least avian Cry1a is directly activated by light (see Figure 5 ).…”

“…This splice product appears to be widespread; by genomic BLAST database search, it was also indicated in more than 25 avian species of various orders ( Einwich et al, 2020 ). Another study localized Cry4 also in the outer plexiform layer, where it seemed associated with the synapses between photoreceptors and horizontal cells ( Hochstoeger et al, 2020 ).…”

“…A possible role of Cry4 in magnetoreception has been frequently discussed (e.g., Günther et al, 2018 ; Pinzon-Rodriguez et al, 2018 ; Hochstoeger et al, 2020 ). Especially its location within the double cones prompted speculations on such a role of Cry4 because of the possibility that the input of two adjacent receptors with the magneto-receptive molecules oriented in different directions could be compared; it was proposed that this might help to overcome problems with different light intensities and polarization ( Worster et al, 2017 ; Günther et al, 2018 ).…”

“…This, together with the gap junctions between the two cones, would interfere with a comparison, making such a role of Cry4 in the double cones rather unlikely. Hochstoeger et al (2020) speculated about a possible role of Cry4 in the outer plexiform layer. The Cry4 in the LWS single cones seems even less suitable for magnetoreception because the red oil droplets in these cones transmit only long wavelengths that cannot photo-reduce cryptochrome.…”

Trendbericht: Elektronen‐Paramagnetische‐Resonanzspektroskopie

“…Zeitaufgelöste EPR und magnetfeldabhängige transiente Absorptionsspektroskopie deuten daraufhin, dass eine solche Navigation der Tiere durch den magnetfeldabhängigen Radikalpaar-Mechanismus möglich sein könnte. 40,41) In-situ-EPR Mit der EPR-Spektroskopie lassen sich chemische Reaktionen auch in situ verfolgen, was Aussagen über die Reaktionsdynamik im Zentrum solcher Arbeiten ermöglicht. Im Zentrum stehen katalytische Reaktionen.…”