Johns Hopkins University School of Medicine, Baltimore, MD, USA.
DIBINEM, University of Bologna, Italy.
FEBS J. 2022 May;289(10):2755-2770. doi: 10.1111/febs.15864. Epub 2021 Apr 22.
Desmin is the primary intermediate filament (IF) of cardiac, skeletal, and smooth muscle. By linking the contractile myofibrils to the sarcolemma and cellular organelles, desmin IF contributes to muscle structural and cellular integrity, force transmission, and mitochondrial homeostasis. Mutations in desmin cause myofibril misalignment, mitochondrial dysfunction, and impaired mechanical integrity leading to cardiac and skeletal myopathies in humans, often characterized by the accumulation of protein aggregates. Recent evidence indicates that desmin filaments also regulate proteostasis and cell size. In skeletal muscle, changes in desmin filament dynamics can facilitate catabolic events as an adaptive response to a changing environment. In addition, post-translational modifications of desmin and its misfolding in the heart have emerged as key determinants of homeostasis and disease. In this review, we provide an overview of the structural and cellular roles of desmin and propose new models for its novel functions in preserving the homeostasis of striated muscles.
结蛋白是心脏、骨骼和平滑肌的主要中间丝（IF）。结蛋白 IF 通过将收缩性肌原纤维与肌膜和细胞细胞器连接，有助于肌肉结构和细胞完整性、力传递和线粒体动态平衡。结蛋白的突变导致肌原纤维排列不齐、线粒体功能障碍和机械完整性受损，从而导致人类的心脏和骨骼肌病，通常表现为蛋白质聚集体的积累。最近的证据表明，结蛋白丝还调节蛋白质稳态和细胞大小。在骨骼肌中，结蛋白丝动力学的变化可以促进分解代谢事件，作为对不断变化的环境的适应性反应。此外，结蛋白的翻译后修饰及其在心脏中的错误折叠已成为维持肌肉内稳态和疾病的关键决定因素。在这篇综述中，我们提供了结蛋白的结构和细胞作用的概述，并提出了其在维持横纹肌内稳态的新功能的新模型。
