Drosophila lowfat, a novel modulator of Fat signaling.

Drosophila lowfat, a novel modulator of Fat signaling.
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DOI:
10.1242/dev.036152
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发表时间:
2009-10
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Irvine KD
Irvine KD
中科院分区:
其他
文献类型:
--
作者:
Mao Y;Kucuk B;Irvine KD

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Fat-Hippo-Warts信号网络调节转录和平面细胞极性。尽管它对生长和平面极性的正常控制至关重要,但我们对调节脂肪的机制只有有限的了解。我们在这里报告的一个保守的细胞质蛋白,低脂,作为脂肪信号的调制器的鉴定。果蝇Lowfat及其人类同源物LIX 1和LIX 1-like与Fat配体Dachsous、受体蛋白Fat及其人类同源物FAT 4的胞质结构域结合。低脂蛋白在椎间盘细胞中定位于亚顶端膜,这种膜定位受脂肪和Dachsous的影响。低脂表达通常沿着发育中的翅膀的背腹边界沿着上调,并且负责那里的脂肪蛋白水平升高。在低脂突变细胞中,脂肪和Dachsous蛋白的水平降低,并且可以通过低脂的过度表达而增加。低脂肪突变动物表现出类似于脂肪的弱等位基因的翅膀表型,并且LFT与脂肪和腊肠犬两者在遗传上相互作用。这些研究确定低脂是脂肪信号通路的一种新成分,LFT介导的脂肪水平升高是调节脂肪信号的一种机制。
The Fat-Hippo-Warts signaling network regulates both transcription and planar cell polarity. Despite its critical importance to the normal control of growth and planar polarity, we have only a limited understanding of the mechanisms that regulate Fat. We report here the identification of a conserved cytoplasmic protein, Lowfat, as a modulator of Fat signaling. Drosophila Lowfat, and its human homologues LIX1 and LIX1-like, bind to the cytoplasmic domains of the Fat ligand Dachsous, the receptor protein Fat, and its human homologue FAT4. Lowfat protein can localize to the sub-apical membrane in disc cells, and this membrane localization is influenced by Fat and Dachsous. Lowfat expression is normally upregulated along the dorsal-ventral boundary of the developing wing, and is responsible for elevated levels of Fat protein there. Levels of Fat and Dachsous protein are reduced in lowfat mutant cells, and can be increased by over-expression of Lowfat. lowfat mutant animals exhibit a wing phenotype similar to weak alleles of fat, and lft interacts genetically with both fat and dachsous. These studies identify Lowfat as a novel component of the Fat signaling pathway, and the Lft-mediated elevation of Fat levels as a mechanism for modulating Fat signaling.
四关节是一种高尔基激酶,可磷酸化钙粘蛋白结构域的子集。
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