Summary Proper regulation of sleep-wake behavior and feeding is essential for organismal health and survival. While previous studies have isolated discrete neural loci and substrates important for either sleep or feeding, how the brain is organized to coordinate both processes with respect to one another remains poorly understood. Here, we provide evidence that the Drosophila Neuropeptide F (NPF) network forms a critical component of both adult sleep and feeding regulation. Activation of NPF signaling in the brain promotes wakefulness and adult feeding, likely through its cognate receptor NPFR. Flies carrying a loss-of-function NPF allele do not suppress sleep following prolonged starvation conditions, suggesting that NPF acts as a hunger signal to keep the animal awake. NPF-expressing cells, specifically those expressing the circadian photoreceptor cryptochrome, are largely responsible for changes to sleep behavior caused by NPF neuron activation, but not feeding, demonstrating that different NPF neurons separately drive wakefulness and hunger.

Lamina-associated polypeptide 2α (LAP2α) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2α interacts with A-type lamins and retinoblastoma protein and regulates cell cycle progression via the E2F-Rb pathway. Using yeast two-hybrid analysis and three independent in vitro binding assays we identified a new LAP2α interaction partner of hitherto unknown functions, which we termed LINT-25. LINT-25 protein levels were upregulated during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation. Upon cell cycle exit LINT-25 accumulated in heterochromatin foci, and LAP2α protein levels were downregulated by proteasomal degradation. Although LAP2α was not required for the upregulation and reorganization of LINT-25 during cell cycle exit, transient expression of LINT-25 in proliferating cells caused loss of LAP2α and subsequent cell death. Our data show a role of LINT-25 and LAP2α during cell cycle exit, in which LINT-25 acts upstream of LAP2α.