Krauss Robert S
Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Adv Exp Med Biol. 2017;1006:361-373. doi: 10.1007/978-4-431-56550-5_22.
Myoblast differentiation is a complex process. As myoblasts differentiate into myofibers, they acquire a cell type-specific transcriptional program, irreversibly exit the cell cycle, and dramatically change their morphology. The morphological changes include cell elongation, alignment, and fusion into syncytial myofibers. Several lines of evidence suggest that these events may be co-regulated. However, the mechanisms that coordinate major alterations in a cell's transcriptome and its shape are not well understood. Muscle-specific transcription is controlled by proteins of the MyoD family, transcription factors whose activity is regulated by specific signal transduction pathways, including the p38 MAP kinase pathway. In a search for genes that might play a role in linking myogenic signal transduction, cytoskeletal regulation, and myoblast differentiation, Dbn1 (encoding the actin regulator drebrin) was identified. Dbn1 expression is induced during myoblast differentiation, in a p38 MAP kinase- and MyoD- dependent manner. RNAi-mediated depletion of drebrin, or treatment with a chemical drebrin inhibitor, resulted in a similar phenotype in myoblasts: defective differentiation, with low levels of early and late differentiation markers and inefficient production of myofibers. Drebrin localizes at sites of cell-cell contact and cell extensions, locations that are also enriched for F-actin. Drebrin may be important in linking transcriptional and morphological aspects of myoblast differentiation.
成肌细胞分化是一个复杂的过程。当成肌细胞分化为肌纤维时，它们会获得一种细胞类型特异性的转录程序，不可逆地退出细胞周期，并显著改变其形态。形态学变化包括细胞伸长、排列以及融合形成多核肌纤维。多项证据表明这些事件可能受到共同调控。然而，协调细胞转录组及其形态重大改变的机制尚未完全清楚。肌肉特异性转录受MyoD家族蛋白控制，这些转录因子的活性由特定信号转导途径调控，包括p38丝裂原活化蛋白激酶途径。在寻找可能在连接成肌信号转导、细胞骨架调控和成肌细胞分化中发挥作用的基因时，发现了Dbn1（编码肌动蛋白调节因子脑桥蛋白）。Dbn1的表达在成肌细胞分化过程中以p38丝裂原活化蛋白激酶和MyoD依赖的方式被诱导。RNA干扰介导的脑桥蛋白缺失或用化学脑桥蛋白抑制剂处理，在成肌细胞中产生了类似的表型：分化缺陷，早期和晚期分化标志物水平低，肌纤维生成效率低下。脑桥蛋白定位于细胞间接触和细胞延伸部位，这些部位也富含F-肌动蛋白。脑桥蛋白可能在连接成肌细胞分化的转录和形态学方面发挥重要作用。
