Nebulin, encoded by NEB, is a giant skeletal muscle protein of about 6669 amino acids which forms an integral part of the sarcomeric thin filament. In recent years, the nebula around this protein has been largely lifted resulting in the discovery that nebulin is critical for a number of tasks in skeletal muscle. In this review, we firstly discussed nebulin’s role as a structural component of the thin filament and the Z-disk, regulating the length and the mechanical properties of the thin filament as well as providing stability to myofibrils by interacting with structural proteins within the Z-disk. Secondly, we reviewed nebulin’s involvement in the regulation of muscle contraction, cross-bridge cycling kinetics, Ca²⁺-homeostasis and excitation contraction (EC) coupling. While its role in Ca²⁺-homeostasis and EC coupling is still poorly understood, a large number of studies have helped to improve our knowledge on how nebulin affects skeletal muscle contractile mechanics. These studies suggest that nebulin affects the number of force generating actin-myosin cross-bridges and may also affect the force that each cross-bridge produces. It may exert this effect by interacting directly with actin and myosin and/or indirectly by potentially changing the localisation and function of the regulatory complex (troponin and tropomyosin). Besides unravelling the biology of nebulin, these studies are particularly helpful in understanding the patho-mechanism of myopathies caused by NEB mutations, providing knowledge which constitutes the critical first step towards the development of therapeutic interventions. Currently, effective treatments are not available, although a number of therapeutic strategies are being investigated.

中文翻译：

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神经蛋白：具有重大责任的大蛋白质。

由NEB编码的Nebulin是大约6669个氨基酸的巨型骨骼肌蛋白，形成了肌节细丝的组成部分。近年来，围绕该蛋白质的星云已被大大提升，导致发现星云蛋白对于骨骼肌的许多任务至关重要。在这篇综述中，我们首先讨论了星云蛋白作为细丝和Z盘结构成分的作用，调节细丝的长度和机械性能，以及通过与Z-内的结构蛋白相互作用为肌原纤维提供稳定性。磁盘。其次，我们回顾了星云蛋白在肌肉收缩，跨桥循环动力学，Ca ^{2+中的参与}-稳态和激发收缩（EC）耦合。尽管其在Ca ²⁺稳态和EC耦合中的作用仍知之甚少，但大量研究有助于提高我们对星云蛋白如何影响骨骼肌收缩力学的认识。这些研究表明，星云蛋白会影响产生肌动蛋白-肌球蛋白横桥的力的数量，也可能会影响每个横桥产生的力。它可能通过直接与肌动蛋白和肌球蛋白相互作用和/或通过潜在地改变调节复合物（肌钙蛋白和原肌球蛋白）的定位和功能而间接发挥这种作用。这些研究除了揭示星云蛋白的生物学特性外，还有助于理解NEB引起的肌病的病理机制。突变，提供知识，这些知识构成了开发治疗干预措施的关键的第一步。当前，尽管正在研究许多治疗策略，但尚无有效的治疗方法。