An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan

Cell. 2008 Dec 26;135(7):1189-200. doi: 10.1016/j.cell.2008.10.018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ankyrins / chemistry
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Costameres / metabolism*
  • Dynactin Complex
  • Dystroglycans / metabolism*
  • Dystrophin / genetics
  • Dystrophin / metabolism*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / metabolism
  • Neuromuscular Junction / metabolism*
  • Sarcolemma / metabolism
  • Sequence Alignment


  • Ank2 protein, mouse
  • Ank3 protein, mouse
  • Ankyrins
  • Dynactin Complex
  • Dystrophin
  • Microtubule-Associated Proteins
  • apo-dystrophin 1
  • Dystroglycans