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: As depicted by the model shown in Figure 10A, we suggest that IFs in partnership with plectin serve NMJs in a dual way. First, they promote and consolidate postsynaptic membrane infolding by being linked to AChR/rapsyn complexes at the crest of the folds and to lateral DGCs along the sides of the folds. Second, by physically connecting the endplate region with myonuclei, mitochondria, and Z-disks (via isoforms P1, P1b, and P1d), IFs provide the stable, and at the same time flexible, subsarcolemmal microenvironment around the folds that guarantees efficient force transmission and mechanosensitivity. In contrast, when IFs retract from the endplates and collapse into aggregates in the absence of plectin, endplates lose their typically folded architecture, mobile AChRs remain loose without forming immobilized clusters, and MTs become more prominent (invading the space normally occupied by IFs; Figure 10B).
Affiliation: Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.