Maturation and maintenance of the neuromuscular synapse: Genetic evidence for roles of the dystrophin-glycoprotein complex

R. Mark Grady, Heather Zhou, Jeanette M. Cunningham, Michael D. Henry, Kevin P. Campbell, Joshua R. Sanes

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

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, α-dystrobrevin (α-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 α-DB or a transmembrane DGC component (dystroglycan). Our resuits suggest that α-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.

Original languageEnglish
Pages (from-to)279-293
Number of pages15
JournalNeuron
Volume25
Issue number2
DOIs
StatePublished - 2000

Fingerprint

Dive into the research topics of 'Maturation and maintenance of the neuromuscular synapse: Genetic evidence for roles of the dystrophin-glycoprotein complex'. Together they form a unique fingerprint.

Cite this