A Circadian Output in Drosophila Mediated by Neurofibromatosis-1 and Ras/MAPK
Top Cited Papers
- 21 September 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 293 (5538) , 2251-2256
- https://doi.org/10.1126/science.1063097
Abstract
Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. InDrosophila, null mutations of theneurofibromatosis-1 (Nf1) gene produce abnormalities of circadian rhythms in locomotor activity. Mutant flies show normal oscillations of the clock genes period(per) and timeless (tim) and of their corresponding proteins, but altered oscillations and levels of a clock-controlled reporter. Mitogen-activated protein kinase (MAPK) activity is increased in Nf1 mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/MAPK pathway. Thus, Nf1 signals through Ras/MAPK inDrosophila. 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, suggesting a coupling of PDF to Ras/MAPK signaling.Keywords
This publication has 25 references indexed in Scilit:
- Molecular Components of the Circadian System in DrosophilaAnnual Review of Physiology, 2001
- Circadian Regulation of cGMP-Gated Cationic Channels of Chick Retinal ConesNeuron, 2001
- Circadian Activation of Bullfrog Retinal Mitogen-activated Protein Kinase Associates with Oscillator FunctionJournal of Biological Chemistry, 2000
- Rescue of a Drosophila NF1 Mutant Phenotype by Protein Kinase AScience, 1997
- A mouse model for the learning and memory deficits associated with neurofibromatosis type INature Genetics, 1997
- Coupling of the RAS-MAPK Pathway to Gene Activation by RSK2, a Growth Factor-Regulated CREB KinaseScience, 1996
- Ras signaling and NF1Current Opinion in Genetics & Development, 1995
- Altered circadian pacemaker functions and cyclic AMP rhythms in the drosophila learning mutant dunceNeuron, 1994
- The Neurofibromatosis Type 1 GeneAnnual Review of Neuroscience, 1993
- The Son of sevenless Gene Product: a Putative Activator of RasScience, 1992