Duan Hong, Nguyen Hanh T
Department of Medicine, Forchheimer G46, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Mol Cell Biol. 2006 Feb;26(4):1414-23. doi: 10.1128/MCB.26.4.1414-1423.2006.
Skeletal muscle formation in Drosophila melanogaster requires two types of myoblasts, muscle founders and fusion-competent myoblasts. Lame duck (Lmd), a member of the Gli superfamily of transcription factors, is essential for the specification and differentiation of fusion-competent myoblasts. We report herein that appropriate levels of active Lmd protein are attained by a combination of posttranscriptional mechanisms. We provide evidence that two different regions of the Lmd protein are critical for modulating the balance between its nuclear translocation and its retention within the cytoplasm. Activation of the Lmd protein is also tempered by posttranslational modifications of the protein that do not detectably change its subcellular localization. We further show that overexpression of Lmd protein derivatives that are constitutively nuclear or hyperactive results in severe muscle defects. These findings underscore the importance of regulated Lmd protein activity in maintaining proper activation of downstream target genes, such as Mef2, within fusion-competent myoblasts.
黑腹果蝇的骨骼肌形成需要两种类型的成肌细胞，即肌肉始祖细胞和具有融合能力的成肌细胞。跛脚鸭（Lmd）是转录因子Gli超家族的成员，对于具有融合能力的成肌细胞的特化和分化至关重要。我们在此报告，活性Lmd蛋白的适当水平是通过转录后机制的组合来实现的。我们提供的证据表明，Lmd蛋白的两个不同区域对于调节其核转运与其在细胞质中的保留之间的平衡至关重要。Lmd蛋白的激活也受到该蛋白翻译后修饰的调节，这些修饰不会明显改变其亚细胞定位。我们进一步表明，组成型核或高活性的Lmd蛋白衍生物的过表达会导致严重的肌肉缺陷。这些发现强调了在具有融合能力的成肌细胞中调节Lmd蛋白活性对于维持下游靶基因（如Mef2）的适当激活的重要性。
