A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK

被引:174
作者
Williams, JA
Su, HS
Bernards, A
Field, J
Sehgal, A [1 ]
机构
[1] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
[4] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA
关键词
D O I
10.1126/science.1063097
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. In Drosophila, null mutations of the neurofibromatosis-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 in Drosophila. 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.
引用
收藏
页码:2251 / 2256
页数:6
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