Cryptochrome clock function

In flies, cryptochrome is clearly involved in mediating hght-induced disruption of the TIM/PER complex. However, the story may not end here. Interestingly, the recent suggestion that cryptochrome in peripheral oscillators (antenna) may play a nonphotic role in clock function in the fly, is analogous to the clear nonphotic role of CRY as a key oschlator component that normally associates with PER in mammals. 

Surprisingly, cryptochrome was not found solely in the retina. In addition to low levels found in all tissues, Cryl was also expressed in the SCN, and Cryl mRNA oscillated with circadian rhythmicity, which indicated an additional role for cryptochrome in circadian clock function. Based on the mRNA expression pattern, we postulated a role for Cry2 in circadian photoreception in the retina as well as a hght-independent role for Cryl in the circadian clock mechanism in the SCN. 

Helfrich-Forster C, Winter C, Hofbauer A, Hall JC, Stanewsky R 2001 The circadian clock of fruit flies is blind after elimination of all known photoreceptors. Neuron 30 249-261 Lin FJ, Song W, Meyer-Bernstein E, Naidoo N, Sehgal A 2001 Photic signaling by cryptochrome in the Drosophilacitcidiaa system. Mol Cell Biol 21 7287-7294 Mas P, Devlin PF, Panda S, Kay SA 2000 Functional Interaction of phytochrome B and cryptochrome 2. Nature 408 207-211... 

Kara R, Wan K, Wakamatsu H et al 2001 Restricted feeding entrains liver clock without participation of the suprachiasmatic nucleus. Genes Cells 6 269—278 Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A 2000 Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci USA 97 14697-14702... 

Ivanchenko M, Stanewsky R, Giebultowicz JM 2001 Circadian photoreception in Drosophila-, functions of cryptochrome in peripheral and central clocks. J Biol Rhythms 16 205-215... 

Cryptochrome genes have been found in many organisms. In the fly Drosophila cryptochrome appears to interact directly with the clock proteins that control the circadian cycle. Most important are products of two genes per (period) and tim (timeless). They are helix-loop-helix DNA binding proteins that form heterodimers, are translocated to the nucleus, and repress their own transcription. Morning light leads to a rapid disappearance of e TIM protein. The cryptochrome CRY appears to react directly with TIM to inactivate it. However, details remain to be learned. " The circadian clock mechanism appears to be universal and the cryptochrome-2 mcryl gene) appears to function in the mouse. A human cDNA clone was found to have a 48% identity with a relative of cryptochromes, the (6-4) photolyase of Drosophila. 

Cryptochrome/photolyase blue light photoreceptor family. The photoreceptors in this family are flavoproteins. They have a wide range of functions including circadian clock regulation, seed germination, and pigment accumulation. 

In contrast to the paucity of biochemical data on the photosensory functions of cryptochromes, there are extensive genetic and cell biology data on the roles of cryptochromes in blue light, photoreception in plants and animals, and circadian clock regulation in animals (Gashmore, 2003 Lin and Shalitin, 2003 Sancar, 2003). In Arabidopsis, blue light inhibits elongation of hypocotyls in a cryptochrome-dependent manner. In animals. 

While cryptochrome s role in the circadian clock mechanism is clear, its light-dependent function remains to be elucidated. The evidence for cryptochrome as a blue-light circadian photoreceptor is the following ... 

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