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Fig. 7. Sarcoglycans and signaling. (A) Schematics of sarcolemma scaffolding in normal and SG^–/– muscle cells. Filamin normally associates with sarcoglycans, but in SG^–/– cells, sarcolemma filamin expression is considerably increased (Thompson et al., 2000). A relationship between cytoskeletal stresses and signaling via phosphorylation is posited. DG, dystroglycan; ECM, extracellular matrix; SG, sarcoglycan. The integrin adhesion complex proteins talin, paxillin, vinculin, etc., may be perturbed by the filamin over-expression, affecting signalling. (B) Proposed signaling circuit that incorporates changes in phosphorylation in SG^–/– tissue (+ or – in red) as well as our in vitro results for contractility and viability. Filamin-B overexpression has been shown to accelerate myotube differentiation (van der Flier et al., 2002) and is also known to influence MAP-kinase signaling (Awata et al., 2001), extending perhaps to ERK-1/2. Filamin also interacts with cvHSP, a homolog of hsp27 (Krief et al., 1999) and (P)-hsp27 is a substrate of (P)-MAPKAPK2 (Ibitayo et al., 1999), which is in turn a substrate of (P)-p38 MAPK (Ryder et al., 2000). Both (P)-hsp27 and (P)-MYPT1/2 are associated with sustained muscle contraction (Ibitayo et al., 1999; Sward et al., 2000). (P)-ERK-1/2 phosphorylates FAK (Carragher et al., 2003). Both (P)-FAK (Laprise et al., 2002) and (P)-ERK-1/2 have been linked to myocyte apoptosis (Cheung and Slack, 2004; Subramaniam et al., 2004). Dashed lines indicate proposed connections, thick lines indicate stretch-induced signals.

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