Potential m-Calpain Substrates during Myoblast Fusion

Cathepsin B localizes to plasma membrane caveolae of differentiating myoblasts and is secreted in an active form at physiological pH

“…The potential for catB interaction with other proteases at the membrane of fusing myoblasts is substantial and longstanding. For example, the non-lysosomal cysteine protease, m-calpain, increases in a fusion-related manner, exhibits a peripheral distribution in fusion-competent myoblasts (Kaur and Sanwal, 1981;Schollmeyer, 1986), and has been implicated in cleavage of the fibronectin network and myoblast cytoskeletal and membrane components, including caveolin-3 (Dourdin et al, 1999;Moyen et al, 2004), while serine proteases -and their receptors, such as uPA, tissue plasminogen activator (tPA) and the a-enolase-type plasminogen receptor (PlgR) -are required for myoblast fusion (Festoff et al, 1986;Lopez-Alemany et al, 2003).…”

“…There is longstanding evidence that many cellular proteases are involved in the structural alterations associated with recognition and fusion events, and that the expression of these proteases is tightly regulated during myogenesis (Kaur and Sanwal, 1981;Guerin and Holland, 1995;Dourdin et al, 1999). Our studies in rat, mouse, and human myoblasts in culture suggest that the lysosomal cysteine protease, cathepsin B (catB), is one these cellular proteases.…”

Myoblast migration is prevented by a calpain‐dependent accumulation of MARCKS

“…Although it has been shown that calpain activity increases during this step of myoblast differentiation Barnoy et al, 1996), µ-and m-calpain do not appear concomitantly, thus suggesting that these proteases may act differently. Previous studies have shown that these proteases can proteolyze many substrates such as myofibrillar proteins (such as troponin and alpha-actin) (Selliah et al, 1996;Mair, 1999) and cytoskeletal associated proteins (such as desmin, vimentin and talin) (Goll et al, 1991;Poussard et al, 1993;Dourdin et al, 1999). Moreover, exteriorization of m-calpain is required for myoblast fusion in order to hydrolyze extracellular matrix components or to cleave the linkage of fibronectin and integrins complexes (Brustis et al, 1993;Dourdin et al, 1997).…”

Disruption of the Murine Calpain Small Subunit Gene, Capn4: Calpain Is Essential for Embryonic Development but Not for Cell Growth and Division

“…Their Ca 2ϩ dependence suggests a link to signal transduction (19), and the common assumption that the calpains become membrane bound on exposure to Ca 2ϩ (35,39) suggests that cytoskeletal proteins may be among the favored substrates. The list of proposed calpain substrates is very long (19,63), and many reports have suggested that calpain may be involved in cell adhesion, spreading, and migration (26,29,49), myoblast fusion (4,11), cell cycle control (36), and mitosis (50). Apoptosis is another cell function for which there are conflicting reports about the involvement of calpain.…”