title: Defective membrane remodeling in neuromuscular diseases: insights from animal models.
abstract: Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.
authors.affiliation: Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
authors.forename: Belinda S
authors.initials: BS
authors.lastname: Cowling
authors.forename: Anne
authors.initials: A
authors.lastname: Toussaint
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C075637:amphiphysin; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin; D034281:Dynamins