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A Photochemical Signal Transduction Model of Magnetoreception in Cryptochrome

Abstract

For decades, scientists have documented the ability of numerous animal species to sense the Earth’s magnetic field. Migratory birds detect and use this magnetic information to navigate their migratory paths. The precise mechanism underlying this apparent biological compass is unkown and remains an active area of ongoing research. A bio-compass based on the chemistry of magnetically sensitive radical pairs is one of the leading theories under investigation. Such chemistry is known to form under illumination in the cryptochrome photoreceptor, which has been found within the retina of migratory birds. This work seeks to create a model that details how a cryptochome-based bio-compass could signal magnetic information. The model developed here considers the physical mechanism by which signal transduction could occur given the unique biology of the cryptochrome protein structure. Further, a quantitative description of cryptochrome magnetic sensitivity and signaling is devised based on well documented, as well as approximated, aspects of the receptor’s photocycle. The functioning threshold for a biologically feasible chemical compass is thus proposed based on a signal-to-noise ratio. Flavin adenine dinucleotide (FAD), the light sensing chromophore of cryptochrome, is widely viewed as a likely site of radical pair chemistry. Using the Runda-Kuta method to solve the first order kinetics of the cryptochrome photocycle provides a baseline for analyzing the effects of different magnetic field orientations on the steady state concentrations of flavin redox states. These concentration fluctuations constitute magnetic information that can be signaled along a neural pathway. Flavin has been found to form radical pairs with tryptophan or superoxide, both potentially magnetically sensitive. Modeling both radical pair formations suggests that a flavin-tryptophan radical pair strongly aligns with light effects observed in behavioral experiments, while a flavin- superoxide does far less so. Still, the model suggests a flavin-superoxide radical pair may have a role in explaining magnetic sensing under dark conditions. The model also suggests further experiments that may elucidate which radical-pair, flavin-tryptophan or flavin-superoxide, and which flavin signaling state, semi-reduced or fully-reduced, contributes most strongly to the magnetic sensitivity of the biological compass.

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