Stanewsky R, Frisch B, Brandes C, Hamblen-Coyle M J, Rosbash M, Hall J C
Department of Biology, Brandeis University, Waltham, Massachusetts 02254, USA.
J Neurosci. 1997 Jan 15;17(2):676-96. doi: 10.1523/JNEUROSCI.17-02-00676.1997.
Rhythmic oscillations of the PER protein, the product of the Drosophila period (per) gene, in brain neurons of the adult fly are strongly involved in the control of circadian rhythms. We analyzed temporal and spatial expression patterns of three per-reporter fusion genes, which share the same 4 kb regulatory upstream region but contain increasing amounts of per's coding region fused in frame to the bacterial lacZ gene. The fusion proteins contained either the N-terminal half (SG), the N-terminal-two-thirds (BG), or nearly all (XLG) of the PER protein. All constructs led to reporter signals only in the known per-expressing cell types within the anterior CNS and PNS. Whereas the staining intensity of SG files was constantly high at different Zeitgeber times, the in situ signals in BG and XLG files cycled with approximately 24 hr periodicity in the PER-expressing brain cells in wild-type and per01 loss of function files. Despite the rhythmic fusion-gene expression within the relevant neurons of per01 BG files, their locomotor activity in light/dark cycling conditions and in constant darkness was identical to that of per01 controls, uncoupling protein cycling from rhythmic behavior. The XLG construct restored weak behavioral rhythmicity to (otherwise) per01 files, indicating that the C-terminal third of PER (missing in BG) is necessary to fulfill the biological function of this clock protein.
果蝇周期(per)基因的产物PER蛋白在成年果蝇脑神经元中的节律性振荡,在昼夜节律的控制中起着重要作用。我们分析了三个per报告基因融合基因的时空表达模式,它们共享相同的4 kb上游调控区域,但包含越来越多的per编码区域,与细菌lacZ基因读框融合。融合蛋白包含PER蛋白的N端一半(SG)、N端三分之二(BG)或几乎全部(XLG)。所有构建体仅在前脑中枢神经系统和外周神经系统中已知的per表达细胞类型中产生报告信号。虽然SG果蝇的染色强度在不同的授时因子时间持续较高,但BG和XLG果蝇的原位信号在野生型和per01功能缺失果蝇的PER表达脑细胞中以约24小时的周期循环。尽管per01 BG果蝇相关神经元内融合基因表达有节律,但它们在光/暗循环条件和持续黑暗中的运动活性与per01对照相同,使蛋白循环与节律行为解偶联。XLG构建体使(否则)per01果蝇恢复了微弱的行为节律性,表明PER的C端三分之一(BG中缺失)对于实现这种生物钟蛋白的生物学功能是必要的。