An extracellular pathway for dystroglycan function in acetylcholine receptor aggregation and laminin deposition in skeletal myotubes

Abstract

The dystroglycan (DG) complex is involved in agrin-induced acetylcholine receptor clustering downstream of muscle-specific kinase where it regulates the stability of acetylcholine receptor aggregates as well as assembly of the synaptic basement membrane. We have previously proposed that this entails coordinate extracellular and intracellular interactions of its two subunits, α- and β-DG. To assess the contribution of the extracellular and intracellular portions of DG, we have used adenoviruses to express full-length and deletion mutants of β-DG in myotubes derived from wild-type embryonic stem cells or from cells null for DG. We show that α-DG is properly glycosylated and targeted to the myotube surface in the absence of β-DG. Extracellular interactions of DG modulate the size and the microcluster density of agrin-induced acetylcholine receptor aggregates and are responsible for targeting laminin to these clusters. Thus, the association of α- and β-DG in skeletal muscle may coordinate independent roles in signaling. We discuss how DG may regulate synapses through extracellular signaling functions of its α subunit. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.