Institute of Physiology II, University of Münster, Germany; Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Germany; German Centre for Cardiovascular Research, Berlin, Germany.
J Biomech. 2023 May;152:111553. doi: 10.1016/j.jbiomech.2023.111553. Epub 2023 Mar 23.
The discovery of the giant protein titin, also known as connectin, dates almost half a century back. In this review, I recapitulate major advances in the discovery of the titin filaments and the recognition of their properties and function until today. I briefly discuss how our understanding of the layout and interactions of titin in muscle sarcomeres has evolved and review key facts about the titin sequence at the gene (TTN) and protein levels. I also touch upon properties of titin important for the stability of the contractile units and the assembly and maintenance of sarcomeric proteins. The greater part of my discussion centers around the mechanical function of titin in skeletal muscle. I cover milestones of research on titin's role in stretch-dependent passive tension development, recollect the reasons behind the enormous elastic diversity of titin, and provide an update on the molecular mechanisms of titin elasticity, details of which are emerging even now. I reflect on current knowledge of how muscle fibers behave mechanically if titin stiffness is removed and how titin stiffness can be dynamically regulated, such as by posttranslational modifications or calcium binding. Finally, I highlight novel and exciting, but still controversially discussed, insight into the role titin plays in active tension development, such as length-dependent activation and contraction from longer muscle lengths.
肌联蛋白（也称为连接蛋白）的发现可以追溯到近半个世纪以前。在这篇综述中，我回顾了肌联蛋白纤维的发现以及对其性质和功能的主要认识进展。我简要讨论了我们对肌节中肌联蛋白的结构和相互作用的理解是如何发展的，并回顾了肌联蛋白基因（TTN）和蛋白水平序列的关键事实。我还提到了肌联蛋白在稳定收缩单位、肌节蛋白组装和维持方面的重要特性。我的讨论主要集中在肌联蛋白在骨骼肌中的机械功能上。我涵盖了肌联蛋白在伸展依赖性被动张力发展中的作用的研究里程碑，回顾了肌联蛋白巨大弹性多样性的原因，并提供了肌联蛋白弹性的分子机制的最新信息，即使在现在，这些细节也在不断涌现。我思考了如果去除肌联蛋白的刚性，肌肉纤维在机械性能上的表现，以及肌联蛋白的刚性如何能够动态调节，例如通过翻译后修饰或钙结合。最后，我强调了肌联蛋白在主动张力发展中所扮演的角色的新的、令人兴奋但仍有争议的见解，例如从更长的肌肉长度产生的长度依赖性激活和收缩。
