Dynamin 2 and human diseases.
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.
Durieux
Anne-Cécile
AC
Inserm, UMR S974, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, F-75013, France.
Prudhon
Bernard
B
Guicheney
Pascale
P
Bitoun
Marc
M
D000818:Animals; D001369:Axons; D002462:Cell Membrane / Q000378:metabolism; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism; D002966:Clathrin / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D034285:Dynamin II / Q000096:biosynthesis / Q000502:physiology*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D005799:Genes, Dominant; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D020914:Myopathies, Structural, Congenital / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000473:pathology
D002966:Clathrin; D034285:Dynamin II