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Molecular and Cellular Biology, November 2001, p. 7287-7294, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7287-7294.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Photic Signaling by Cryptochrome in the Drosophila Circadian System

Fang-Ju Lin, Wei Song, Elizabeth Meyer-Bernstein, Nirinjini Naidoo, and Amita Sehgal*

Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

Received 25 January 2001/Returned for modification 5 March 2001/Accepted 7 August 2001

Oscillations of the period (per) and timeless (tim) gene products are an integral part of the feedback loop that underlies circadian behavioral rhythms in Drosophila melanogaster. Resetting this loop in response to light requires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlying the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light response. Light-induced TIM ubiquitination precedes CRY degradation and is increased when electron transport is blocked. Thus, inhibition of electron transport may "lock" CRY in an active state by preventing signaling required either to degrade CRY or to convert it to an inactive form. High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA 19104. Phone: (215) 573-2985. Fax: (215) 573-2015. E-mail: amita{at}mail.med.upenn.edu.

Molecular and Cellular Biology, November 2001, p. 7287-7294, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7287-7294.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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