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Acetylcholine receptors are required for agrin‐induced clustering of postsynaptic proteins
Author(s) -
Marangi P.Angelo,
Forsayeth John R.,
Mittaud Peggy,
ErbVögtli Susanne,
Blake Derek J.,
Moransard Martijn,
Sander Andreas,
Fuhrer Christian
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.24.7060
Subject(s) - agrin , postsynaptic potential , acetylcholine receptor , biology , utrophin , microbiology and biotechnology , neuromuscular junction , neuroscience , receptor , biochemistry , cytoskeleton , cell
We have investigated the role of acetylcholine receptors (AChRs) in an early step of postsynaptic assembly at the neuromuscular synapse, the clustering of postsynaptic proteins induced by nerve‐released agrin. To achieve this, we used two variants of C2 myotubes virtually lacking AChRs and C2 cells in which surface AChRs were down‐regulated by AChR antibodies. In all cases, agrin caused normal clustering of the agrin receptor component MuSK, α‐dystrobrevin and utrophin, but failed to aggregate AChRs, α‐ and β‐dystroglycan, syntrophin isoforms and rapsyn, an AChR–anchoring protein necessary for postsynaptic assembly and AChR clustering. In C2 variants, the stability of rapsyn was decreased, whereas in antibody‐treated cells, rapsyn efficiently co‐localized with remaining AChRs in microaggregates. Upon ectopic injection into myofibers in vivo , rapsyn did not form clusters in the absence of AChRs. These results show that AChRs and rapsyn are interdependent components of a pre‐assembled protein complex that is required for agrin‐induced clustering of a full set of postsynaptic proteins, thus providing evidence for an active role of AChRs in postsynaptic assembly.