Drosophila crinkled, mutations of which disrupt morphogenesis and cause lethality, encodes fly myosin VIIA
Drosophila crinkled, mutations of which disrupt morphogenesis and cause lethality, encodes fly myosin VIIA
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DOI：
10.1534/genetics.104.026369
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发表时间：
2004-11-01
期刊：
影响因子：
3.3
通讯作者：
Ashburner, M
中科院分区：
文献类型：
--
作者：
Kiehart, DP;Franke, JD;Ashburner, M
肌球蛋白vii为广泛的真核生物过程提供运动功能。我们证明褶皱（ck）的突变破坏了果蝇肌球蛋白VIIA重链。在整个果蝇发育过程中，ck/myoVIIA蛋白水平较低，在头、胸和腹部也有相同水平。严重的ck等位基因，可能是分子零，在胚胎或幼虫时死亡，但迄今为止测试的所有等位基因组合产生的一小部分成年“逃脱者”是虚弱和不育的。扫描电子显微镜显示，逃脱者在鬃毛和毛发上有缺陷，表明这种运动蛋白在肌动蛋白细胞骨架的结构中起作用。我们建立了ck/myosin VIIA头部结构的同源性模型，表明myosin VIIA与myosin ii一样，在其N端前有一个类似谱蛋白的SH3亚结构域。此外，我们确定了两个肌球蛋白VIIA FERM重复序列与典型的FERM结构域的三叶结构的前两个子结构域具有高度的序列相似性。然而，在第一个和第二个FERM结构域的前两个裂片后面的类似于100和类似于75的氨基酸在肌球蛋白vii中是高度保守的，这表明它们组成了一个保守的肌球蛋白尾部同源7 （MyTH7）结构域，可能是FERM结构域的一个组成部分，也可能独立于FERM结构域起作用。总之，我们的数据表明，ck/myoVIIA在细胞突起的形成和生存所需的其他基于肌动蛋白的功能中起着关键作用。
Myosin VIIs provide motor function for a wide range of eukaryotic processes. We demonstrate that mutations in crinkled, (ck) disrupt the Drosophila myosin VIIA heavy chain. The ck/myoVIIA protein is present at a low level throughout fly development and at the same level in heads, thoraxes, and abdomens. Severe ck alleles, likely to be molecular nulls, die as embryos or larvae, but all allelic combinations tested thus far yield a small fraction of adult "escapers" that are weak and infertile. Scanning electron microscopy shows that escapers have defects in bristles and hairs, indicating that this motor protein plays a role in the structure of the actin cytoskeleton. We generate a homology model for the structure of the ck/myosin VIIA head that indicates myosin VIIAs, like myosin IIs, have a spectrin-like, SH3 subdomain fronting their N terminus. In addition, we establish that the two myosin VIIA FERM repeats share high sequence similarity with only the first two subdomains of the three-lobed structure that is typical of canonical FERM domains. Nevertheless, the similar to100 and similar to75 amino acids that follow the first two lobes of the first and second FERM domains are highly conserved among myosin VIIs, suggesting that they compose a conserved myosin tail homology 7 (MyTH7) domain that may be an integral part of the FERM domain or may function independently of it. Together, our data suggest a key role for ck/myoVIIA in the formation of cellular projections and other actin-based functions required for viability.