Forced expression of dystrophin deletion constructs reveals structure-function correlations.

• DOI: 10.1083/jcb.134.1.93
• Publication Date: 2004-05-15T01:23:47Z
• Authors: J A Rafael; G A Cox; K Corrado; D Jung; K P Campbell; J S Chamberlain
• Keywords: Dystroglycan; Utrophin; Sarcolemma

Dystrophin plays an important role in skeletal muscle by linking the cytoskeleton and extracellular matrix. The amino terminus of dystrophin binds to actin possibly other components subsarcolemmal cytoskeleton, while carboxy associates with a group integral peripheral membrane proteins glycoproteins that are collectively known as dystrophin-associated protein (DAP) complex. We have generated transgenic/mdx mice expressing "full-length" constructs, but consecutive deletions within COOH-terminal domains. These enabled analysis interaction between members DAP complex effects perturbing these associations on dystrophic process. Deletions cysteine-rich region disrupt complex, leading severe pathology. remove beta-dystroglycan-binding site, which leads parallel loss both beta-dystroglycan sarcoglycan from sarcolemma. In contrast, deletion alternatively spliced domain extreme COOH has no apparent effect function when expressed at normal levels. resulting latter two supported formation completely their expression was associated morphology mdx mice. data indicate is critical for functional activity, presumably mediating direct beta-dystroglycan. However, remainder not required assembly