Defective membrane remodeling in neuromuscular diseases: Insights from animal models

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. © 2012 cowling et al.