Muscle dystroglycan organizes the postsynapse and regulates presynaptic neurotransmitter release at the Drosophila neuromuscular junction.
BACKGROUND
The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila.


RESULTS
We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site.


CONCLUSIONS
Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg.
Bogdanik
Laurent
L
CNRS, UMR 5203, Institut de Génomique fonctionnelle, Montpellier, France.
Framery
Bérénice
B
Frölich
Andreas
A
Franco
Bénédicte
B
Mornet
Dominique
D
Bockaert
Joël
J
Sigrist
Stephan J
SJ
Grau
Yves
Y
Parmentier
Marie-Laure
ML
D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D049030:Dystroglycans / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D017470:Receptors, Glutamate / Q000378:metabolism; D013049:Spectrin / Q000378:metabolism
D029721:Drosophila Proteins; D016189:Dystrophin; D007797:Laminin; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D017470:Receptors, Glutamate; C442474:cora protein, Drosophila; D013049:Spectrin; D049030:Dystroglycans