InsP(3) receptor is essential for growth and differentiation but not for vision in Drosophila

InsP(3) receptor is essential for growth and differentiation but not for vision in Drosophila
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DOI:
10.1016/s0896-6273(00)80328-1
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发表时间:
1997-06-01
期刊:
影响因子:
16.2
通讯作者:
Zuker, CS
Zuker, CS
中科院分区:
医学1区
文献类型:
--
作者:
Acharya, JK;Jalink, K;Zuker, CS

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磷脂酶C (PLC)是两种主要信号转导途径的焦点:一种是由G蛋白偶联受体启动的,另一种是由酪氨酸激酶受体启动的。活性PLC水解磷脂酰肌醇二磷酸(PIP2)为两个第二信使肌醇1,4,5-三磷酸(InsP(3))和二酰基甘油(DAG)。DAG激活蛋白激酶C,而InsP(3)通过InsP(3)受体从细胞内调动钙。[Ca2+]的变化(i)调节多种靶蛋白的功能,包括离子通道、激酶、磷酸酶、蛋白酶和转录因子(Berridge, 1993)。在小鼠中,有三个InsP(3)R基因,1型InsP(3)R突变体表现为共济失调和癫痫发作(Matsumoto et al., 1996)。在果蝇中,只有一个InsP(3)受体(InsP(3)R)基因是已知的,它在整个发育过程中普遍表达(Hasan and Rosbash, 1992; Yoshikawa et al., 1992; Raghu and Hasan, 1995)。在这里,我们描述了果蝇InsP(3)R突变体,并证明了InsP(3)R在胚胎和幼虫发育中是必不可少的。有趣的是,母体InsP(3)R mRNA足以在胚胎阶段进行发育,但幼虫器官表现出不同步和有缺陷的细胞分裂,并且成像盘早期停止并无法分化。我们还生成了成年马赛克动物,并证明了光导,一种被认为需要InsP(3)R的模型PLC通路,不需要InsP(3)R来发出信号。
Phospholipase C (PLC) is the focal point for two major signal transduction pathways: one initiated by G protein-coupled receptors and the other by tyrosine kinase receptors. Active PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into the two second messengers inositol 1,4,5-trisphosphate (InsP(3)) and diacyl glycerol (DAG). DAG activates protein kinase C, and InsP(3) mobilizes calcium from intracellular stores via the InsP(3) receptor. Changes in [Ca2+](i) regulate the function of a wide range of target proteins, including ion channels, kinases, phosphatases, proteases, and transcription factors (Berridge, 1993). In the mouse, there are three InsP(3)R genes, and type 1 InsP(3)R mutants display ataxia and epileptic seizures (Matsumoto et al., 1996). In Drosophila, only one InsP(3) receptor (InsP(3)R) gene is known, and it is expressed ubiquitously throughout development (Hasan and Rosbash, 1992; Yoshikawa et al., 1992; Raghu and Hasan, 1995). Here, we characterize Drosophila InsP(3)R mutants and demonstrate that the InsP(3)R is essential for embryonic and larval development. Interestingly, maternal InsP(3)R mRNA is sufficient for progression through the embryonic stages, but larval organs show asynchronous and defective cell divisions, and imaginal discs arrest early and fail to differentiate. We also generated adult mosaic animals and demonstrate that phototransduction, a model PLC pathway thought to require InsP(3)R, does not require InsP(3)R for signaling.