DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment
DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment
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DOI：
10.1242/dev.047589
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发表时间：
2012-05-15
期刊：
影响因子：
4.6
通讯作者：
Noselli, Stephane
中科院分区：
文献类型：
--
作者：
Petzoldt, Astrid G.;Coutelis, Jean-Baptiste;Noselli, Stephane
在双侧，内脏器官的定位和环行需要适当的左右(L/R)不对称的建立。最近在果蝇中发现了一个新的反转位点基因，编码非常规型ID肌球蛋白(MyoID)。在myoid突变果蝇中，L/R轴是反向的，导致器官如肠道、输卵管和生殖器的反向循环。我们之前已经证明MyoID与β-连环素具有物理上的相互作用，这表明粘着连接在果蝇L/R不对称中起到了作用。在这里，我们证明了DE-钙粘附素与MyoID共沉淀，并且是MyoID L/R活动所必需的。我们进一步证明，MyoIC是一种密切相关的非常规I型肌球蛋白，在体外和体内都可以通过阻止其与黏附连接成分的结合来拮抗MyoID L/R的活性。有趣的是，DE-钙粘附素抑制MyoIC，为MyoID功能提供保护机制。条件遗传学实验表明，DE-钙粘附素、MyoIC和MyoID在L/R不对称中的作用具有时间同步性。这些数据表明，在粘连连接处被β-连环蛋白募集MyoID后，DE-钙粘附素通过促进MyoID活性和抑制MyoIC活性，对果蝇L/R不对称具有双重作用。有趣的是，脊椎动物Situs inversus基因逆转蛋白的产物也与β-连环素发生物理相互作用，这表明粘连连接可能是决定因素建立L/R不对称的保守平台，在脊椎动物和无脊椎动物中都是如此。
In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with beta-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by beta-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with beta-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.