Inserm, UMR S974, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, F-75013, France.
J Mol Med (Berl). 2010 Apr;88(4):339-50. doi: 10.1007/s00109-009-0587-4. Epub 2010 Feb 3.
Dynamin 2 (DNM2) mutations cause autosomal dominant centronuclear myopathy, a rare form of congenital myopathy, and intermediate and axonal forms of Charcot-Marie-Tooth disease, a peripheral neuropathy. DNM2 is a large GTPase mainly involved in membrane trafficking through its function in the formation and release of nascent vesicles from biological membranes. DNM2 participates in clathrin-dependent and clathrin-independent endocytosis and intracellular membrane trafficking (from endosomes and Golgi apparatus). Recent studies have also implicated DNM2 in exocytosis. DNM2 belongs to the machinery responsible for the formation of vesicles and regulates the cytoskeleton providing intracellular vesicle transport. In addition, DNM2 tightly interacts with and is involved in the regulation of actin and microtubule networks, independent from membrane trafficking processes. We summarize here the molecular, biochemical, and functional data on DNM2 and discuss the possible pathophysiological mechanisms via which DNM2 mutations can lead to two distinct neuromuscular disorders.
动力蛋白 2（DNM2）突变导致常染色体显性中核肌病，这是一种罕见的先天性肌病，以及中间型和轴索性腓骨肌萎缩症，一种周围神经病。DNM2 是一种大型 GTPase，主要通过其在生物膜中形成和释放新生囊泡的功能参与膜运输。DNM2 参与网格蛋白依赖性和非网格蛋白依赖性内吞作用以及细胞内膜运输（从内体和高尔基体）。最近的研究还表明 DNM2 参与胞吐作用。DNM2 属于负责囊泡形成的机制，并调节细胞骨架提供细胞内囊泡运输。此外，DNM2 与肌动蛋白和微管网络紧密相互作用并参与其调节，与膜运输过程无关。在这里，我们总结了关于 DNM2 的分子、生化和功能数据，并讨论了 DNM2 突变如何导致两种不同的神经肌肉疾病的可能病理生理机制。
