New pathway to understanding circadian rhythms

The mechanism that keeps track of time in our body is based on a perpetual secretion of clock proteins in a 24-hour feedback loop. But the signaling molecules that control this clock are largely unknown. In September 21 Science Julie Williams and colleagues from Howard Hughes Medical Institute, show that that the protein produced by Drosophila version of the neurofibromatosis-1 (Nf1) gene controls the circadian machinery via the Ras/MAPK signaling pathway.

Williams et al. studied Drosophila with non-functioning mutations of the Nf1 gene and found that this produced flies with circadian rhythm abnormalities in locomotor activity. Mutant flies showed altered oscillations and levels of a clock-controlled reporter and had increased activity of mitogen-activated protein kinase (MAPK). In addition, immunohistochemical staining revealed a circadian oscillation of phospho-MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, which suggests a coupling of PDF to Ras/MAPK ...