Devl. Biol. 227: 595-605 (2000)
Dystroglycan is a member of the transmembrane dystrophin
glycoprotein complex in muscle that binds to the
synapse-organizing molecule agrin. Dystroglycan binding and AChR
aggregation are mediated by two separate domains of agrin. To
test whether dystroglycan plays a role in receptor aggreg ation
at the neuromuscular junction, we overexpressed it by injecting
rabbit dystroglycan RNA into one or two-celled Xenopus
embryos. We measured AChR aggregation in myotomes by labeling
them with rhodamine-a-bungarotoxin
followed by confocal microscopy and image analysis. Dystroglycan
overexpression decreased AChR aggregation at the neuromuscular
junction. This result is consistent with dystroglycan competition
for agrin without signaling AChR aggregation. It also supports
the hypothesis that dystroglycan is not the myotube-associated
specificity component (MASC), a putative co-receptor needed for
agrin to activate muscle-specific kinase (MuSK) and signal AChR
aggregation. Dystroglycan was distributed along the surface of
muscle membranes, but was concentrated at the ends of myotomes,
where AChRs normally aggregate at synapses. Overexpressed
dystroglycan altered AChR aggregation in a rostral-caudal
gradient, consistent with the sequential development of
neuromuscular synapses along the embryo. Increasing
concentrations of dystroglycan RNA did not further decrease AChR
aggregation, but decreased embryo survival. Development often
stopped during gastrulation, suggesting an essential,
non-synaptic role of dystroglycan during this early period of
development.