An unconventional myosin in Drosophila reverses the default handedness in visceral organs
An unconventional myosin in Drosophila reverses the default handedness in visceral organs
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DOI：
10.1038/nature04625
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发表时间：
2006-04-06
期刊：
影响因子：
64.8
通讯作者：
Matsuno, K
中科院分区：
文献类型：
--
作者：
Hozumi, S;Maeda, R;Matsuno, K
动物的内脏器官常常存在左右不对称(1,2)。尽管果蝇前后轴和背腹轴的形成已被充分了解，但左右不对称性尚未得到广泛研究。在这里，我们发现，在可存活且可生育的纯合 Myo31DF 突变体中，胚胎肠道以及成年肠道和睾丸的旋手性是相反的（不是随机的）。 Myo31DF 编码一种非常规的肌球蛋白，果蝇 MyoIA（在哺乳动物中也称为 MyoID；参考文献 3、4），并且是第一个与左右模式相关的基于肌动蛋白的运动蛋白。我们发现后肠上皮需要 Myo31DF 来维持正常的胚胎用手习惯。后肠上皮中肌动蛋白丝的破坏使胚胎肠道的手性随机化，表明 Myo31DF 功能需要肌动蛋白细胞骨架。与此一致的是，我们发现 Myo31DF 与细胞骨架共定位。另一种肌球蛋白 I（参考文献 4）Myo61F 的过度表达可逆转胚胎肠道的手性，其敲低还会导致左右模式缺陷。这两种非常规肌球蛋白 I 蛋白可能在左右模式中具有拮抗功能。我们认为肌动蛋白细胞骨架和肌球蛋白 I 蛋白可能对于无脊椎动物产生左右不对称性至关重要。
The internal organs of animals often have left - right asymmetry(1,2). Although the formation of the anterior - posterior and dorsal ventral axes in Drosophila is well understood, left - right asymmetry has not been extensively studied. Here we find that the handedness of the embryonic gut and the adult gut and testes is reversed ( not randomized) in viable and fertile homozygous Myo31DF mutants. Myo31DF encodes an unconventional myosin, Drosophila MyoIA ( also referred to as MyoID in mammals; refs 3, 4), and is the first actin-based motor protein to be implicated in left - right patterning. We find that Myo31DF is required in the hindgut epithelium for normal embryonic handedness. Disruption of actin filaments in the hindgut epithelium randomizes the handedness of the embryonic gut, suggesting that Myo31DF function requires the actin cytoskeleton. Consistent with this, we find that Myo31DF colocalizes with the cytoskeleton. Overexpression of Myo61F, another myosin I ( ref. 4), reverses the handedness of the embryonic gut, and its knockdown also causes a left - right patterning defect. These two unconventional myosin I proteins may have antagonistic functions in left - right patterning. We suggest that the actin cytoskeleton and myosin I proteins may be crucial for generating left - right asymmetry in invertebrates.