Yue Li, Michael Rosbash

Phase resetting by light is an important feature of circadian rhythms, and the current Drosophila model focuses on light-mediated degradation of the clock protein TIMELESS (TIM). PERIOD (PER) is the binding partner of TIM and a major repressor of the molecular clock, but direct evidence of PER in phase resetting is lacking. Because light sensitivity of the per(S) short period mutant strain is strongly enhanced compared with wild-type strains, we assayed the importance of PER degradation for light-induced phase shifting. The per(S) protein (PERS) is markedly less stable than wild-type PER, in tissue culture and in flies, and PERS as well as PER is stabilized by TIM in both systems. Consistent with this finding, light-induced TIM degradation appears to trigger PER degradation. Moreover, TIM degradation is similar in the clock neurons of both strains, suggesting that it is not strongly affected by PERS and does not dictate the difference in the light response. In contrast, there is a dramatic quantitative difference between PER and PERS degradation in these neurons, indicating that PER degradation dictates the enhanced amplitude of the light-induced phase response. The data indicate that TIM inhibits PER degradation and that PER degradation follows light-mediated TIM degradation within circadian neurons; PER degradation then dictates qualitative as well as quantitative features of light-mediated phase-resetting.