Obscurin is required for the lateral alignment of striated myofibrils in zebrafish
Obscurin is required for the lateral alignment of striated myofibrils in zebrafish
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DOI：
10.1002/dvdy.20812
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发表时间：
2006-08-01
影响因子：
2.5
通讯作者：
Russell, Mark W.
中科院分区：
文献类型：
--
作者：
Raeker, Maide O.;Su, Fengyun;Russell, Mark W.
Obscurin/obscurin-MLCK是一种巨大的肌节相关蛋白，具有多种亚型，其与肌联蛋白和小锚蛋白-1的相互作用表明其在肌原纤维组装、结构支持和肌浆网的肌节排列中具有重要作用。在这项研究中，我们的特点是斑马鱼的直向同源物obscurin和研究其在横纹肌原纤维大会的作用。斑马鱼obscurin在受精后24小时（hpf）在体节和中枢神经系统中表达，48 hpf在心脏中表达。使用两个独立的吗啉代反义寡核苷酸消耗obscurin导致骨骼肌原纤维的数量减少和明显的混乱，受损的相邻肌原纤维的横向排列，肌浆网的解体，体节分割缺陷，心脏结构和功能异常。这是首次证明obscurin是脊椎动物心脏和骨骼肌发育所必需的。响应于obscurin耗尽而产生和组织新肌原纤维的能力减弱表明，它可能在心脏和骨骼肌病的病因或适应中起重要作用。
Obscurin/obscurin-MLCK is a giant sarcomere-associated protein with multiple isoforms whose interactions with titin and small ankyrin-1 suggest that it has an important role in myofibril assembly, structural support, and the sarcomeric alignment of the sarcoplasmic reticulum. In this study, we characterized the zebrafish orthologue of obscurin and examined its role in striated myofibril assembly. Zebrafish obscurin was expressed in the somites and central nervous system by 24 hours post-fertilization (hpf) and in the heart by 48 hpf. Depletion of obscurin using two independent morpholino antisense oligonucleotides resulted in diminished numbers and marked disarray of skeletal myofibrils, impaired lateral alignment of adjacent myofibrils, disorganization of the sarcoplasmic reticulum, somite segmentation defects, and abnormalities of cardiac structure and function. This is the first demonstration that obscurin is required for vertebrate cardiac and skeletal muscle development. The diminished capacity to generate and organize new myofibrils in response to obscurin depletion suggests that it may have a vital role in the causation of or adaptation to cardiac and skeletal myopathies.