Circadian rhythms exist to coordinate an organism's physiological and behavioral processes with the solar light/dark cycle. Dysfunctional circadian rhythms have been implicated in several psychiatric and sleep disorders and current light-based therapies have only limited success. Photoreceptors are required to convey light information to the molecular clock in the brain in order to synchronize its oscillation with the solar cycle. Both opsins and UV/blue light-absorbing cryptochromes have been identified as circadian photoreceptors in mammals. Recently, a UV/blue light photoreceptor was shown to induce clock gene expression in response to light in the zebrafish Z3 cell line. The main goal of this proposal is to determine if cryptochromes act as circadian photoreceptors in zebrafish and determine their mechanism of signal transduction using the Z3 cell line. This will be accomplished by: 1) determining the role of zebrafish cryptochromes in light-dependent gene induction using RNA interference; 2) characterizing the spectrometric properties of the zebrafish cryptochromes; and 3) identifying proteins that interact with zebrafish cryptochromes in a light-modulated manner. The results from these experiments will further our understanding of the role of cryptochromes in circadian phototransduction and will provide the groundwork for future studies in mammalian systems that will benefit the design of new circadian-based therapeutics for psychiatric and sleep disorders.
| Partch, Carrie L; Shields, Katherine F; Thompson, Carol L et al. (2006) Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. Proc Natl Acad Sci U S A 103:10467-72 |
| Partch, Carrie L; Sancar, Aziz (2005) Cryptochromes and circadian photoreception in animals. Methods Enzymol 393:726-45 |
| Partch, Carrie L; Clarkson, Michael W; Ozgur, Sezgin et al. (2005) Role of structural plasticity in signal transduction by the cryptochrome blue-light photoreceptor. Biochemistry 44:3795-805 |
