title: Maturation and maintenance of the neuromuscular synapse: genetic evidence for roles of the dystrophin--glycoprotein complex.
abstract: The dystrophin-glycoprotein complex (DGC) links the cytoskeleton of muscle fibers to their extracellular matrix. Using knockout mice, we show that a cytoplasmic DGC component, alpha-dystrobrevin (alpha-DB), is dispensable for formation of the neuromuscular junction (NMJ) but required for maturation of its postsynaptic apparatus. We also analyzed double and triple mutants lacking other cytoskeletal DGC components (utrophin and dystrophin) and myotubes lacking a alpha-DB or a transmembrane DGC component (dystroglycan). Our results suggest that alpha-DB acts via its linkage to the DGC to enhance the stability of postsynaptic specializations following their DGC-independent formation; dystroglycan may play additional roles in assembling synaptic basal lamina. Together, these results demonstrate involvement of distinct protein complexes in the formation and maintenance of the synapse and implicate the DGC in the latter process.
authors.affiliation: Department of Pediatrics, Washington University Medical School, St. Louis, Missouri 63110, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Grady
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: J M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: M D
authors.initials: MD
authors.lastname: Henry
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
authors.forename: J R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D016189:Dystrophin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D009363:Neoplasm Proteins; D009469:Neuromuscular Junction / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding / Q000502:physiology; D011950:Receptors, Cholinergic / Q000032:analysis / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D049411:Utrophin
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D006023:Glycoproteins; D007797:Laminin; D008565:Membrane Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D011950:Receptors, Cholinergic; C491632:Sspn protein, mouse; C483600:Utrn protein, mouse; D049411:Utrophin; C098885:dystrobrevin; C091824:syntrophin