Cryptochromes in Mammals and Birds: Clock or Magnetic Compass?

Species throughout the animal kingdom use the Earth's magnetic field (MF) to navigate using either or both of two mechanisms. The first relies on magnetite crystals in tissue where their magnetic moments align with the MF to transduce a signal transmitted to the central nervous system. The second and the subject of this paper involves cryptochrome (CRY) proteins located in cone photoreceptors distributed across the retina, studied most extensively in birds. According to the "Radical Pair Mechanism" (RPM), blue/UV light excites CRY's flavin cofactor (FAD) to generate radical pairs whose singlet-to-triplet interconversion rate is modulated by an external MF. The signaling product of the RPM produces an impression of the field across the retinal surface. In birds, the resulting signal on the optic nerve is transmitted along the thalamofugal pathway to the primary visual cortex, which projects to brain regions concerned with image processing, memory, and executive function. The net result is a bird's orientation to the MF's inclination: its vector angle relative to the Earth's surface. The quality of ambient light (e.g., polarization) provides additional input to the compass. In birds, the Type IV CRY isoform appears pivotal to the compass, given its positioning within retinal cones; a cytosolic location therein indicating no role in the circadian clock; relatively steady diurnal levels (unlike Type II CRY's cycling); and a full complement of FAD (essential for photosensitivity). The evidence indicates that mammalian Type II CRY isoforms play a light-independent role in the cellular molecular clock without a photoreceptive function.