Disease relevance of CRY2

• CRY2 immunoreactivity was detected in most cells in the ganglion cell layer (GCL) and in a subset of cells in the inner nuclear layer (INL) in both the macula and periphery [1].
• We tested Cry1-/- Cry2-/- mice and fibroblasts derived from these mice for radiation-induced cancer and killing and DNA damage checkpoints and killing, respectively [2].

Psychiatry related information on CRY2

• Here we show that mice lacking the Cryl or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively [3].

High impact information on CRY2

• Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms [3].
• The mammalian proteins Cryl and Cry2, which are members of the family of plant blue-light receptors (cryptochromes) and photolyases, have been proposed as candidate light receptors for photoentrainment of the biological clock [3].
• Light-independent role of CRY1 and CRY2 in the mammalian circadian clock [4].
• Previous experiments in our lab have identified a type III RPTP, CRYP-2/cPTPRO, specifically expressed during the period of axon outgrowth in the chick brain; cPTPRO is expressed in the axons and growth cones of retinal and tectal projection neurons [5].
• CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons in vitro [5].

Biological context of CRY2

• We have now identified a second human gene whose amino acid sequence displays 73% identity to the first one and have named the two genes CRY1 and CRY2, respectively [6].
• Database searches have identified Medicago truncatula expressed sequence tags (ESTs) corresponding to all three genes, whereas only a single CRY2 is represented in EST collections from the more distantly related legumes soybean and Lotus japonicus [7].
• Phylogenetic analyses show at least 2 rounds of gene duplication at the base of the metazoan radiation, as well as several losses, gave rise to 2 cryptochrome (cry) gene families in insects, a Drosophila-like cry1 gene family and a vertebrate-like cry2 family [8].
• At a molecular level, light pulse exposure during the night led to an up-regulation of Per1 and Per2 concomitant with a down-regulation of Cry2 in the suprachiasmatic nucleus of A. ansorgei [9].
• The cloned rat cry2 cDNA consists of 2,131 nucleotides and has a single open-reading frame that encodes the rat CRY2 of 594 amino acids with start and stop codons [10].

Anatomical context of CRY2

• To analyze the patterns of expression of the cryptochromes, CRY1 and CRY2, in the human retina and to correlate expression of these putative blue-light receptors with nonvisual photoreceptor localization [1].

Associations of CRY2 with chemical compounds

• By mapping the functional data onto a cryptochrome/6-4 photolyase gene tree, we find that the transcriptional repressive function of insect CRY2 descended from a light-sensitive photolyase-like ancestral gene, probably lacking the ability to repress CLOCK:CYCLE-mediated transcription [8].
• The corresponding proteins hCRY1 and hCRY2 were purified and characterized as maltose-binding fusion proteins [6].
• Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity [11].
• Phytochromes function as serine/threonine kinases whose potential interacting partners include cryptochrome (CRY1 and CRY2) [12].
• We find that hCRY2 exhibits fluorescence properties consistent with the presence of folate and flavin cofactors [13].

Other interactions of CRY2

• This study demonstrates that light exposure during the subjective night has opposite effects on the expression of the clock genes Per1 and Per2 compared with that of Cry2 [9].

Analytical, diagnostic and therapeutic context of CRY2

• CRY2 protein expression was examined by immunohistochemistry in cross sections of human retina, and its subcellular localization was determined by immunoblot analysis of fractionated human retinal extracts [1].
• CRY1 and CRY2 mRNA expression was analyzed in 4-mm diameter punches of macula and midperipheral human retina by quantitative RT-PCR [1].
• PCR with total DNA from strain J112 and specific primers for cry1, cry2, cry3, cry4, and cyt2A genes revealed that cry1, cry3A, cry4, cry5 and cyt2a genes are present [14].
• A Northern blot analysis showed that rat cry2 was expressed in all of the tissues examined [10].
• In situ hybridization in the whole brain indicated that the strong signal of cry2 mRNA is mainly present in the suprachiasmatic nucleus (SCN) region, but very weak in other brain regions [10].

References