The PDZ-Containing Unconventional Myosin XVIIIA Regulates Embryonic Muscle Integrity in Zebrafish
The PDZ-Containing Unconventional Myosin XVIIIA Regulates Embryonic Muscle Integrity in Zebrafish
复制标题
含有 PDZ 的非常规肌球蛋白 XVIIIA 调节斑马鱼胚胎肌肉的完整性
DOI：
10.1016/j.jgg.2014.06.008
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发表时间：
2014-08-20
影响因子：
5.9
通讯作者：
Shi, Deli
中科院分区：
文献类型：
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作者：
Cao, Jianmeng;Li, Shangqi;Shi, Deli
肌球蛋白XVIIIA或MYO 18 A是一种独特的含有PDZ结构域的非常规肌球蛋白，从果蝇到脊椎动物在进化上是保守的。虽然有证据表明它在体节中表达，但它是否调节肌肉功能仍不清楚。我们发现，这两个斑马鱼myo 18 a基因（myo 18 aa和myo 18 ab）主要表达在体节边界在早期发育阶段。这些基因的敲除或MYO 18 A PDZ结构域的过表达破坏肌纤维完整性，诱导肌纤维病变，并损害肌营养不良蛋白、α-肌营养不良蛋白聚糖（α-DG）和层粘连蛋白在肌节边界的定位。细胞移植实验表明，myo 18 a变形成肌细胞不能在野生型胚胎的肌节中形成细长的肌纤维，这可以通过全长MYO 18 A蛋白来挽救。这些结果表明MYO 18 A可能在粘附过程中起作用，该粘附过程在早期发育期间维持肌纤维与ECM（细胞外基质）的稳定附着和肌肉完整性。
Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function remains unclear. We show that the two zebrafish myo18a genes (myo18aa and myo18ab) are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, alpha-dystroglycan (alpha-DG) and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM (extracellular matrix) and muscle integrity during early development.