Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein.
Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein.
复制标题
通过删除 Toll 蛋白中富含亮氨酸的细胞外重复序列，实现果蝇胚胎的腹侧化。
DOI：
10.1091/mbc.6.5.587
复制
发表时间：
1995
影响因子：
3.3
通讯作者：
Hashimoto,C
中科院分区：
文献类型：
--
作者：
Winans,KA;Hashimoto,C
果蝇胚胎的背腹极性是通过一个信号转导途径建立的，其中母体跨膜蛋白Toll似乎作为腹侧定位的细胞外配体的受体发挥作用。某些显性Toll等位基因编码的蛋白质表现为部分配体非依赖性受体，导致含有这些蛋白质的胚胎变得腹侧化。在来自携带这些显性等位基因的母亲的胚胎提取物中，除了全长Toll多肽与Toll抗体外，我们还检测到约35 kDa的多肽。我们的生化分析表明，较小的多肽是一个截短形式的Toll缺乏胞外结构域序列。为了测定这种缩短形式的Toll的生物活性，我们合成了编码缺乏富含亮氨酸的重复序列的突变多肽的RNA，所述富含亮氨酸的重复序列包含Toll的大部分细胞外结构域，并将该RNA注射到胚胎中。截短的Toll蛋白引起最腹侧细胞的命运独立的野生型Toll蛋白及其配体。这些结果支持了Toll是一种受体，其胞外结构域调节其胞质结构域的内在信号传导活性的观点。
Dorsoventral polarity of the Drosophila embryo is established by a signal transduction pathway in which the maternal transmembrane protein Toll appears to function as the receptor for a ventrally localized extracellular ligand. Certain dominant Toll alleles encode proteins that behave as partially ligand-independent receptors, causing embryos containing these proteins to become ventralized. In extracts of embryos derived from mothers carrying these dominant alleles, we detected a polypeptide of approximately 35 kDa in addition to full-length Toll polypeptides with antibodies to Toll. Our biochemical analyses suggest that the smaller polypeptide is a truncated form of Toll lacking extracellular domain sequences. To assay the biological activity of such a shortened form of Toll, we synthesized RNA encoding a mutant polypeptide lacking the leucine-rich repeats that comprise most of Toll's extracellular domain and injected this RNA into embryos. The truncated Toll protein elicited the most ventral cell fate independently of the wild-type Toll protein and its ligand. These results support the view that Toll is a receptor whose extracellular domain regulates the intrinsic signaling activity of its cytoplasmic domain.