title: An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan.
abstract: beta-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 beta-DG. Dystrophin binds ankyrin-B and ankyrin-G, while beta-DG binds ankyrin-G. Dystrophin and beta-DG require ankyrin-G for retention at costameres but not delivery to the sarcolemma. Dystrophin and beta-DG remain intracellular in ankyrin-B-depleted muscle, where beta-DG accumulates in a juxta-TGN compartment. The neuromuscular junction requires ankyrin-B for localization of dystrophin/utrophin and beta-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.
authors.affiliation: Howard Hughes Medical Institute and Departments of Cell Biology, Biochemistry, and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Gai
authors.initials: G
authors.lastname: Ayalon
authors.forename: Jonathan Q
authors.initials: JQ
authors.lastname: Davis
authors.forename: Paula B
authors.initials: PB
authors.lastname: Scotland
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054974:Costameres / Q000378:metabolism*; D000072159:Dynactin Complex; D049030:Dystroglycans / Q000378:metabolism*; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C498995:Ank2 protein, mouse; C094681:Ank3 protein, mouse; D017487:Ankyrins; D000072159:Dynactin Complex; D016189:Dystrophin; D008869:Microtubule-Associated Proteins; C085339:apo-dystrophin 1; D049030:Dystroglycans