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A more recent version of this article appeared on December 1, 2007
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Submitted on July 2, 2007
Revised on September 13, 2007
Accepted on September 14, 2007
Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109
Monitoring Editor: Yu-li Wang
CAP is an adaptor protein that interacts with both signaling and cytoskeletal proteins. Here we characterize the expression, localization and potential function of CAP in striated muscle. CAP is markedly induced during myoblast differentiation, and colocalizes with vinculin during costamerogenesis. In adult mice, CAP is enriched in oxidative muscle fibers, and is found in membrane anchorage complexes including intercalated discs, costameres and myotendinous junctions. Using both yeast-2-hybrid and proteomic approaches, we identified the sarcomeric protein, filamin C (FLNc) as a binding partner for CAP. When overexpressed, CAP recruits FLNc to cell-extracellular matrix adhesions, where the two proteins cooperatively regulate actin reorganization. Moreover, overexpression of CAP inhibits FLNc-induced cell spreading on fibronectin. In dystrophin-deficient mdx mice, the expression and membrane localization of CAP is increased, concomitant with the elevated plasma membrane content of FLNc, suggesting that CAP may compensate for the reduced membrane linkage of the myofibrils due to the loss of the dystroglycan-sarcoglycan complex in these mice. Thus, through its interaction with FLNc, CAP provides another link between the myofibril cytoskeleton and the plasma membrane of muscle cells, and may play a dynamic role in the regulation and maintenance of muscle structural integrity.