Conservation of the Notch antagonist Hairless in arthropods: functional analysis of the crustacean Daphnia pulex Hairless gene
Conservation of the Notch antagonist Hairless in arthropods: functional analysis of the crustacean Daphnia pulex Hairless gene
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DOI：
10.1007/s00427-017-0593-4
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发表时间：
2017-08
影响因子：
2.4
通讯作者：
A. Zehender;Melanie Bayer;Milena Bauer;B. Zeis;A. Preiss;D. Maier
中科院分区：
文献类型：
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作者：
A. Zehender;Melanie Bayer;Milena Bauer;B. Zeis;A. Preiss;D. Maier
Notch信号通路在所有动物后生动物中都是高度保守的：一旦Notch受体激活，Notch靶基因的转录就会被以转录因子CSL为中心的激活复合体启动。在没有信号的情况下，CSL组装转录抑制复合体，表现出显著的进化多样性。昆虫中Notch信号的主要拮抗剂无毛最初是在果蝇中发现的，它与果蝇无毛的CSL同源抑制物[SU(H)]结合，并招募两个通用的共抑制物Groucho和C-末端结合蛋白。虽然大多数Notch信号成分在昆虫和脊椎动物之间是保守的，但无毛只在昆虫中发现。在这里，我们提出了分析的无毛基因从水蚤，因此，第一次从甲壳类动物。水蚤和果蝇的无毛蛋白序列高度分化。然而，已知的功能结构域，如SU(H)，Groucho和C末端结合蛋白相互作用结构域，是非常保守的。此外，还检测到Daphnia无毛蛋白与果蝇相互作用伙伴的直接结合，证明了分子水平上的保守性。此外，在体内证实了无毛蝙蝠和果蝇SU(H)之间的相互作用，因为在果蝇发育过程中，各自基因的共同过度表达导致了果蝇Notch活性的预期下调。结构模型表明，丝虫和果蝇的无毛-SU(H)阻遏复合体几乎无法相互区分。无毛SU(H)复合体中直接接触的氨基酸残基在两个同系物中处于完全相同的位置。
The Notch signaling pathway is highly conserved in all animal metazoa: upon Notch receptor activation, transcription of Notch target genes is turned on by an activator complex that centers on the transcription factor CSL. In the absence of signal, CSL assembles transcriptional repression complexes that display remarkable evolutionary diversity. The major antagonist of Notch signaling in insects named Hairless was originally identified inDrosophila melanogaster.It binds to theDrosophilaCSL homologue Suppressor of Hairless [Su(H)] and recruits the two general co-repressors, Groucho and C-terminal binding protein. Whereas the majority of Notch signaling components is conserved between insects and vertebrates, Hairless is found only in insects. Here, we present the analysis of theHairlessgene fromDaphnia pulexand, hence, for the first time from a crustacean.DaphniaandDrosophilaHairless protein sequences are highly diverged. Known functional domains, however, the Su(H), Groucho and the C-terminal binding protein interactions domains, are well conserved. Moreover, direct binding of theDaphniaHairless protein and the respectiveDrosophilainteraction partners was detected, demonstrating the conservation at the molecular level. In addition, interaction betweenDaphniaHairless andDrosophilaSu(H) was demonstrated in vivo, as co-overexpression of the respective genes duringDrosophiladevelopment resulted in the expected downregulation of Notch activity in the fly. Structural models show that the Hairless-Su(H) repressor complexes fromDaphniaandDrosophilaare almost indistinguishable from one another. Amino acid residues in direct contact within the Hairless-Su(H) complex are at absolutely identical positions in the two homologues.