Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Clocks / genetics*
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Biological Clocks / radiation effects
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Circadian Rhythm / genetics*
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Circadian Rhythm / radiation effects
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / physiology*
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Glutamic Acid / metabolism
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Light
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Light Signal Transduction / drug effects
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Light Signal Transduction / genetics
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Mutation / genetics
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Neuropeptide Y / metabolism
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Pertussis Toxin / pharmacology
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Photic Stimulation
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Receptors, N-Methyl-D-Aspartate / metabolism
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Retinal Ganglion Cells / cytology
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Retinal Ganglion Cells / metabolism*
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Retinal Ganglion Cells / radiation effects
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Suprachiasmatic Nucleus / cytology
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Suprachiasmatic Nucleus / metabolism*
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Suprachiasmatic Nucleus / radiation effects
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics
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Visual Pathways / cytology
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Visual Pathways / metabolism*
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Visual Pathways / radiation effects
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ras Proteins / genetics
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ras Proteins / physiology*
Substances
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Neuropeptide Y
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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Pertussis Toxin
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Mitogen-Activated Protein Kinases
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GTP-Binding Proteins
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Rasd1 protein, mouse
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GTP-Binding Protein alpha Subunits, Gi-Go
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ras Proteins