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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carrier Proteins / analysis
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cells, Cultured
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Cytoskeletal Proteins / analysis
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Cytoskeleton / genetics
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Cytoskeleton / metabolism
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Dystrophin / analysis
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Dystrophin / genetics
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Dystrophin / metabolism*
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Dystrophin-Associated Proteins*
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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Laminin / analysis
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Laminin / metabolism
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Membrane Proteins / analysis
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred mdx
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Muscle Fibers, Skeletal / cytology
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Muscle Proteins / analysis
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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Mutagenesis / physiology
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Neoplasm Proteins*
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Neuromuscular Junction / chemistry
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Neuromuscular Junction / growth & development
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Neuromuscular Junction / metabolism*
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Phenotype
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Protein Binding / physiology
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Receptors, Cholinergic / analysis
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Receptors, Cholinergic / metabolism
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Synapses / chemistry
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Synapses / metabolism*
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Utrophin
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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Dystrophin
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Dystrophin-Associated Proteins
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Glycoproteins
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Laminin
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Membrane Proteins
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Muscle Proteins
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Neoplasm Proteins
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Receptors, Cholinergic
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Sspn protein, mouse
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Utrn protein, mouse
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Utrophin
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dystrobrevin
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syntrophin