Dexras1 potentiates photic and suppresses nonphotic responses of the circadian clock.
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.
Cheng
Hai-Ying M
HY
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna. hymcheng@yahoo.ca
Obrietan
Karl
K
Cain
Sean W
SW
Lee
Bo Young
BY
Agostino
Patricia V
PV
Joza
Nicholas A
NA
Harrington
Mary E
ME
Ralph
Martin R
MR
Penninger
Josef M
JM
D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000528:radiation effects; D002940:Circadian Rhythm / Q000235:genetics* / Q000528:radiation effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D008027:Light; D055537:Light Signal Transduction / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009478:Neuropeptide Y / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010775:Photic Stimulation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
D009478:Neuropeptide Y; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C498511:Rasd1 protein, mouse; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D018631:ras Proteins