Scube2 mediates Hedgehog signalling in the zebrafish embryo
Scube2 mediates Hedgehog signalling in the zebrafish embryo
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DOI：
10.1016/j.ydbio.2006.02.032
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发表时间：
2006-06-01
影响因子：
2.7
通讯作者：
Currie, Peter D.
中科院分区：
文献类型：
--
作者：
Hollway, Georgina E.;Maule, John;Currie, Peter D.
Hedgehog家族分泌的形态原决定了无脊椎动物和脊椎动物胚胎中大量不同细胞类型的命运，包括斑马鱼胚胎肌节的肌肉细胞前体。Hedgehog敏感肌肉命运的形成在“You”类纯合斑马鱼突变体中被打乱，其中大多数打乱了Hedgehog(HH)信号转导途径的组成部分。我们已经对其中一个突变体You进行了表型和分子表征，我们展示了哺乳动物基因scube2的斑马鱼同源基因突变的结果。该基因编码Scube蛋白家族的一个成员，该家族由几个蛋白质基序组成，包括EGF和Cub结构域。上位论和分子分析将Scube2的功能定位在HH受体复合体的信号成分Smoothens(Smoh)的上游，这表明Scube2可能在HH信号转导过程中发挥作用，在质膜上接收HH信号之前或期间。为了支持这一模型，我们发现Scube2与Cubilin具有同源性，后者编码一种参与蛋白质转运的内吞受体，提示Scube2在HH信号转导中可能的功能模式。(C)2006 Elsevier Inc.保留所有权利。
The Hedgehog family of secreted morphogens specifies the fate of a large number of different cell types within invertebrate and vertebrate embryos, including the muscle cell precursors of the embryonic myotome of zebrafish. Formation of Hedgehog-sensitive muscle fates is disrupted within homozygous zebrafish mutants of the "you"-type class, the majority of which disrupt components of the Hedgehog (HH) signal transduction pathway. We have undertaken a phenotypic and molecular characterisation of one of these mutants, you, which we show results from mutations within the zebrafish orthologue of the mammalian, gene scube2. This gene encodes a member of the Scube family of proteins, which is characterised by several protein motifs including EGF and CUB domains. Epistatic and molecular analyses position Scube2 function upstream of Smoothened (Smoh), the signalling component of the HH receptor complex, suggesting that Scube2 may act during HH signal transduction prior to, or during, receipt of the HH signal at the plasma membrane. In support of this model we show that scube2 has homology to cubilin, which encodes an endocytic receptor involved in protein trafficking suggesting a possible mode of function for Scube2 during HH signal transduction. (c) 2006 Elsevier Inc. All rights reserved.