TY - JOUR
T1 - Maturation and maintenance of the neuromuscular synapse
T2 - Genetic evidence for roles of the dystrophin-glycoprotein complex
AU - Grady, R. Mark
AU - Zhou, Heather
AU - Cunningham, Jeanette M.
AU - Henry, Michael D.
AU - Campbell, Kevin P.
AU - Sanes, Joshua R.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health and the Muscular Dystrophy Association (J. R. S., K. P. C., and R. M. G.). We thank Mia Nichol and James Gross of the Neuroscience Transgenic Facility. K. P. C. is an Investigator of the Howard Hughes Medical Institute.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033757623&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80894-6
DO - 10.1016/S0896-6273(00)80894-6
M3 - Article
C2 - 10719885
AN - SCOPUS:0033757623
SN - 0896-6273
VL - 25
SP - 279
EP - 293
JO - Neuron
JF - Neuron
IS - 2
ER -