Membrane traffic and muscle: lessons from human disease

Abstract

Like all mammalian tissues, skeletal muscle is dependent on membrane traffic for proper development and homeostasis. This fact is underscored by the observation that several human diseases of the skeletal muscle are caused by mutations in gene products of the membrane trafficking machinery. An examination of these diseases and the proteins that underlie them is instructive both in terms of determining disease pathogenesis and of understanding the normal aspects of muscle biology regulated by membrane traffic. This review highlights our current understanding of the trafficking genes responsible for human myopathies.

Figure 1. Centronuclear Myopathy

A–B. Shown are photomicrographs from hematoxylin/eosin stained muscle from an unaffected child (A) and a child with myotubular myopathy (B). Note the small fiber size and the abundant central nuclei (arrows). (images courtesy of Jeff Golden, M.D., University of Pennsylvania) C. List of the genes associated with centronuclear myopathy.

Figure 2. Mutations in Centronuclear Myopathy

A. List of mutations in Dynamin 2. Note that all reported sequence changes are confined to the middle and PH domains. Note that the E368Q mutation* causes both myopathy and peripheral neuropathy(67). B. List of mutations in Amphiphysin 2 (see text for more description).