Neuromuscular synapse integrity requires linkage of acetylcholine receptors to postsynaptic intermediate filament networks via rapsyn-plectin 1f complexes.
Bottom Line: Live imaging of acetylcholine receptors (AChRs) in cultured myotubes differentiated ex vivo from immortalized plectin-deficient myoblasts revealed them to be highly mobile and unable to coalesce into stable clusters, in contrast to wild-type cells.In their phenotypic behavior, mutant mice closely mimicked EBS-MD-MyS patients, including impaired body balance, severe muscle weakness, and reduced life span.Our study demonstrates that linkage to desmin IF networks via plectin is crucial for formation and maintenance of AChR clusters, postsynaptic NMJ organization, and body locomotion.
Affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.Show MeSH
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Mentions: To investigate whether plectin deficiency affected the ultrastructure of NMJs, in particular the typical infoldings of the sarcolemma, we subjected epoxy resin–embedded ultrathin sections of soleus muscle from adult wt and Pax7-Cre/cKO mice to electron microscopy. Whereas in wt mice, the postsynaptic region was characterized by numerous, evenly distributed infoldings of uniform depth, in Pax7-Cre/cKO mice, synaptic infoldings were strikingly rare and of uneven shape (Figure 8, A, left and center, and B). In addition, a dearth of postsynaptic mitochondria was noticeable (Figure 8, A, right, and C).
Affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.