Mutations that impair Eyes absent tyrosine phosphatase activity in vitro reduce robustness of retinal determination gene network output in Drosophila.
Mutations that impair Eyes absent tyrosine phosphatase activity in vitro reduce robustness of retinal determination gene network output in Drosophila.
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DOI：
10.1371/journal.pone.0187546
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Rebay I
中科院分区：
文献类型：
--
作者：
Davis TL;Hoi CSL;Rebay I
有限的信号网络和转录效应物的集合指导了构成发育的细胞行为的全谱。调节潜能多样化的一种机制是将多种生化活动结合到同一蛋白质中。作为模块化原理的例证，Eyes absent （Eya）最初被认为是视网膜决定基因网络（RDGN）中的转录共激活因子，也具有酪氨酸和苏氨酸磷酸酶活性。尽管越来越多的证据表明Eya的磷酸酶活性对哺乳动物生物学的重要性，但在果蝇身上进行的遗传拯救实验表明，酪氨酸磷酸酶的功能对正常发育是必不可少的。在本研究中，我们在减少一种或多种RDGN因子剂量的遗传致敏背景下重复了这些拯救实验。作为RDGN核心成员的sine oculis或dachshund的杂合性降低了磷酸酶死亡的eya的能力，但不影响对照野生型eya转基因，以挽救视网膜缺陷和降低与视力丧失相关的生存能力。我们推测，Eya的酪氨酸磷酸酶活性，虽然不是必需的，赋予RDGN输出稳健性。
A limited collection of signaling networks and transcriptional effectors directs the full spectrum of cellular behaviors that comprise development. One mechanism to diversify regulatory potential is to combine multiple biochemical activities into the same protein. Exemplifying this principle of modularity, Eyes absent (Eya), originally identified as a transcriptional co-activator within the retinal determination gene network (RDGN), also harbors tyrosine and threonine phosphatase activities. Although mounting evidence argues for the importance of Eya’s phosphatase activities to mammalian biology, genetic rescue experiments in Drosophila have shown that the tyrosine phosphatase function is dispensable for normal development. In this study, we repeated these rescue experiments in genetically sensitized backgrounds in which the dose of one or more RDGN factor was reduced. Heterozygosity for sine oculis or dachshund, both core RDGN members, compromised the ability of phosphatase-dead eya, but not of the control wild type eya transgene, to rescue the retinal defects and reduced viability associated with eya loss. We speculate that Eya’s tyrosine phosphatase activity, although non-essential, confers robustness to RDGN output.
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