Dexras1 Potentiates Photic and Suppresses Nonphotic Responses of the Circadian Clock

• DOI: 10.1016/j.neuron.2004.08.021
• Publication Date: 2005-02-17T03:36:05Z
• Authors: Hai-Ying M. Cheng; Karl Obrietan; Sean W. Cain; Bo Young Lee; Patricia V. Agostino; Nicholas A. Joza; Mary E. Harrington; Martin R. Ralph; Josef M. Penninger
• Keywords: Mice, Knockout; Retinal Ganglion Cells; 0301 basic medicine; Light Signal Transduction; Light; Neuroscience(all); Glutamic Acid; GTP-Binding Protein alpha Subunits, Gi-Go; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Circadian Rhythm; Mice; 03 medical and health sciences; Pertussis Toxin; Biological Clocks; GTP-Binding Proteins; Mutation; Animals; Neuropeptide Y; Suprachiasmatic Nucleus; Visual Pathways; Mitogen-Activated Protein Kinases; Photic Stimulation

Circadian rhythms of physiology and behavior are generated by biological clocks that are synchronized to the cyclic environment by photic or nonphotic cues. The interactions and integration of various entrainment pathways to the clock are poorly understood. Here, we show that the Ras-like G protein Dexras1 is a critical modulator of the responsiveness of the master clock to photic and nonphotic inputs. Genetic deletion of Dexras1 reduces photic entrainment by eliminating a pertussis-sensitive circadian response to NMDA. Mechanistically, Dexras1 couples NMDA and light input to Gi/o and ERK activation. In addition, the mutation greatly potentiates nonphotic responses to neuropeptide Y and unmasks a nonphotic response to arousal. Thus, Dexras1 modulates the responses of the master clock to photic and nonphotic stimuli in opposite directions. These results identify a signaling molecule that serves as a differential modulator of the gated photic and nonphotic input pathways to the circadian timekeeping system.