Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development in Drosophila
Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development in Drosophila
复制标题
DOI：
10.1534/genetics.115.174698
复制
发表时间：
2015-02
期刊：
影响因子：
3.3
通讯作者：
T. Okumura;Takeshi Sasamura;Momoko Inatomi;Shunya Hozumi;Mitsutoshi Nakamura;Ryo Hatori;Kiichiro Taniguchi;Naotaka Nakazawa;E. Suzuki;Reo Maeda;Tomoko Yamakawa;K. Matsuno
中科院分区：
文献类型：
--
作者：
T. Okumura;Takeshi Sasamura;Momoko Inatomi;Shunya Hozumi;Mitsutoshi Nakamura;Ryo Hatori;Kiichiro Taniguchi;Naotaka Nakazawa;E. Suzuki;Reo Maeda;Tomoko Yamakawa;K. Matsuno
I类肌球蛋白基因在多种生物中是保守的，其基因产物参与肌动蛋白动力学、内吞作用和信号转导。果蝇有三个I类肌球蛋白基因，肌球蛋白31 DF（Myo 31 DF），肌球蛋白61 F（Myo 61 F）和肌球蛋白95 E（Myo 95 E）。Myo 31 DF、Myo 61 F和Myo 95 E分别属于肌球蛋白ID、肌球蛋白IC和肌球蛋白IB家族。先前对Myo 31 DF和Myo 61 F的功能丧失分析分别揭示了其在左右（LR）不对称发育和肠上皮细胞维持中的重要作用。然而，由于潜在的冗余活性，很难阐明它们在体内的作用。在这里，我们产生了I类肌球蛋白的双重和三重突变体来解决这个问题。我们发现，三重突变体是可行的和可育的，这表明所有三个I类肌球蛋白的生存能力。功能丧失分析进一步揭示，Myo 31 DF和Myo 61 F，而不是Myo 95 E，在促进男性生殖器的右LR不对称发育中具有冗余功能。已知Myo 61 F过表达拮抗Myo 31 DF在各种果蝇器官中的右旋活性。因此，LR逆转活性过表达的Myo 61 F可能不反映其生理功能。在雄性生殖器中观察到Myo 61 F促进右旋LR不对称发育的内源性活性，但在胚胎肠道（另一个LR不对称器官）中未观察到。因此，Myo 61 F和Myo 31 DF，但不是Myo 95 E，发挥组织特异性，冗余的LR不对称发展的作用。我们的研究还揭示了差异共定位的I类肌球蛋白与丝状（F）-肌动蛋白在刷状缘的肠上皮细胞。
The class I myosin genes are conserved in diverse organisms, and their gene products are involved in actin dynamics, endocytosis, and signal transduction. Drosophila melanogaster has three class I myosin genes, Myosin 31DF (Myo31DF), Myosin 61F (Myo61F), and Myosin 95E (Myo95E). Myo31DF, Myo61F, and Myo95E belong to the Myosin ID, Myosin IC, and Myosin IB families, respectively. Previous loss-of-function analyses of Myo31DF and Myo61F revealed important roles in left–right (LR) asymmetric development and enterocyte maintenance, respectively. However, it was difficult to elucidate their roles in vivo, because of potential redundant activities. Here we generated class I myosin double and triple mutants to address this issue. We found that the triple mutant was viable and fertile, indicating that all three class I myosins were dispensable for survival. A loss-of-function analysis revealed further that Myo31DF and Myo61F, but not Myo95E, had redundant functions in promoting the dextral LR asymmetric development of the male genitalia. Myo61F overexpression is known to antagonize the dextral activity of Myo31DF in various Drosophila organs. Thus, the LR-reversing activity of overexpressed Myo61F may not reflect its physiological function. The endogenous activity of Myo61F in promoting dextral LR asymmetric development was observed in the male genitalia, but not the embryonic gut, another LR asymmetric organ. Thus, Myo61F and Myo31DF, but not Myo95E, play tissue-specific, redundant roles in LR asymmetric development. Our studies also revealed differential colocalization of the class I myosins with filamentous (F)-actin in the brush border of intestinal enterocytes.