XXXX Spaghetti and Doubletime Link the Circadian Clock and Light to Caspases, Apoptosis and @entity13859 .

@entity1 @entity137 @entity19123 @entity13859 @entity146 @entity71985 @entity5624 @entity179 @entity238
UNASSIGNED: While circadian dysfunction and @entity179 are correlated, the mechanism for this is not understood. It is not known if age-dependent circadian dysfunction leads to @entity179 , and the proteins that mediate the effect remain unidentified. Here, we show that the knock-down of a regulator (spag) of the circadian kinase Dbt in circadian cells lowers Dbt levels abnormally, lengthens circadian rhythms and causes expression of activated initiator caspase ( @entity71985 ) in the optic lobes during the middle of the day or after light pulses at night. Likewise, reduced Dbt activity lengthens circadian period and causes expression of activated @entity71985 , and a loss-of-function mutation in @entity19123 also leads to expression of activated @entity71985 in a light-dependent manner. Genetic epistasis experiments place Dbt downstream of Spag in the pathway, and Spag-dependent reductions of Dbt are shown to require the proteasome. Importantly, activated @entity71985 expression due to reduced Spag or Dbt activity occurs in cells that do not express the spag RNAi or dominant negative Dbt and requires PDF neuropeptide signaling from the same neurons that support behavioral rhythms. Furthermore, reduction of Dbt or Spag activity leads to @entity71985 -dependent @entity238 @entity5624 cleavage and enhanced @entity179 produced by @entity1 Tau in a @entity238 eye model for @entity13859 . Aging flies with lowered Dbt or Spag function show markers of cell death as well as @entity146 and shortened lifespans, and even old wild type flies exhibit Dbt modification and activated caspase at particular times of day. These results suggest that Dbt suppresses expression of activated @entity71985 to prevent Tau cleavage, and that the circadian clock defects confer sensitivity to expression of activated @entity71985 in response to prolonged light. They establish a link between the circadian clock factors, light, cell death pathways and Tau @entity137 , potentially via dysregulation of circadian neuronal remodeling in the optic lobes.
