Annexin VII relocalization as a result of dystrophin deficiency

Annexin VII (synexin) is a member of the annexin family of proteins, which are characterized by Ca(2+)-dependent binding to phospholipids. In normal skeletal muscle annexin VII is located preferentially at the plasma membrane and the t-tubule system [Selbert et al. (1995) J. Cell. Sci. 108, 85-95]. Here we have analyzed the distribution of annexin VII in muscle disorders in which the Ca2+ regulation is affected. A remarkable difference was observed in muscle specimens from patients suffering from Duchenne muscular dystrophy and also in muscle from the MDX mouse where annexin VII was gradually released from the sarcolemmal membrane into the cytosol and into the extracellular space during progression of the disease. Hypercontracted muscle fibers positive in Ca2+ staining were devoid of cytosolic annexin VII. Annexins IV and VI were similarly released into the extracellular space. Whereas normal skeletal muscle showed specifically the 51-kDa annexin VII isoform, in dystrophic muscle different ratios of the 51-kDa and the muscle-atypic 47-kDa isoforms were observed. The potential of annexin VII to serve as a tool with which cellular Ca2+ levels can be studied and different muscular disorders classified is discussed.