Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2037833 | Cell | 2008 | 12 Pages |
Summaryβ-dystroglycan (DG) and the dystrophin-glycoprotein complex (DGC) are localized at costameres and neuromuscular junctions in the sarcolemma of skeletal muscle. We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and β-DG. Dystrophin binds ankyrin-B and ankyrin-G, while β-DG binds ankyrin-G. Dystrophin and β-DG require ankyrin-G for retention at costameres but not delivery to the sarcolemma. Dystrophin and β-DG remain intracellular in ankyrin-B-depleted muscle, where β-DG accumulates in a juxta-TGN compartment. The neuromuscular junction requires ankyrin-B for localization of dystrophin/utrophin and β-DG and for maintenance of its postnatal morphology. A Becker muscular dystrophy mutation reduces ankyrin binding and impairs sarcolemmal localization of dystrophin-Dp71. Ankyrin-B also binds to dynactin-4, a dynactin subunit. Dynactin-4 and a subset of microtubules disappear from sarcolemmal sites in ankyrin-B-depleted muscle. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.