Cryptochrome: The second photoactive pigment in the eye and its role in circadian photoreception

Circadian rhythms are oscillations in the biochemical, physiological, and b ehavioral functions of organisms that occur with a periodicity of approxima tely 24 h. They are generated by a molecular clock that is synchronized wit h the solar day by environmental photic input. The cryptochromes are the ma mmalian circadian photoreceptors. They absorb light and transmit the electr omagnetic signal to the molecular clock using a pterin and Ravin adenine di nucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and m ice have two cryptochrome genes, CRY1 and CRY2, that are differentially exp ressed in the retina relative to the opsin-based visual photoreceptors. CRY 1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either C ry1 or Cry2 have impaired light induction of the clock gene mPer1 and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in mPer1 induction by light and lacks m olecular and behavioral rhythmicity in constant darkness. Thus, cryptochrom es are photoreceptors and central components of the molecular clock. Generi c evidence also shows that cryptochromes are circadian photoreceptors in Dr osophila and Arabidopsis, raising the possibility that they may be universa l circadian photoreceptors. Research on cryptochromes may provide new under standing of human diseases such as seasonal affective disorder and delayed sleep phase syndrome.