ANNEXIN-VII RELOCALIZATION AS A RESULT OF DYSTROPHIN DEFICIENCY

Annexin VII (synexin) is a member of the annexin family of proteins, w hich are characterized by Ca2+-dependent binding to phospholipids. In normal skeletal muscle annexin Vn: is located preferentially at the pl asma membrane and the t-tubule system [Selbert et al. (1995) J. Cell. Sci. 108, 85-95]. Here we have analyzed the distribution of annexin VI I in muscle disorders in which the Ca2+ regulation is affected. A rema rkable difference was observed in muscle specimens from patients suffe ring from Duchenne muscular dystrophy and also in muscle from the MDX mouse where annexin VII was gradually released from the sarcolemmal me mbrane into the cytosol and into the extracellular space during progre ssion of the disease, Hypercontracted muscle fibers positive in Ca2+ s taining were devoid of cytosolic annexin VII. Annexins IV and VI. were similarly released into the extracellular space. Whereas normal skele tal muscle showed specifically the 51-kDa annexin VII isoform, in dyst rophic 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 mus cular disorders classified is discussed. (C) 1995 Academic Press, Inc.