Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-106
Fuhrer, C; Gautam, M; Sugiyama, J E; Hall, Z W (1999). Roles of rapsyn and agrin in interaction of postsynaptic proteins with acetylcholine receptors. Journal of Neuroscience, 19(5):6405-6416.
At the neuromuscular junction, aggregates of acetylcholine receptors (AChRs) are anchored in the muscle membrane by association with rapsyn and other postsynaptic proteins. We have investigated the interactions between the AChR and these proteins in cultured C2 myotubes before and after treatment with agrin, a nerve-derived protein that induces AChRs to cluster. When AChRs were isolated from detergent extracts of untreated C2 myotubes, they were associated with rapsyn and, to a lesser degree, with utrophin, beta-dystroglycan, MuSK, and src-related kinases, but not with syntrophin. Treatment with agrin increased the association of AChRs with MuSK, a receptor tyrosine kinase that forms part of the agrin receptor complex, without affecting other interactions. Analysis of rapsyn-deficient myotubes, which do not form protein clusters in response to agrin, revealed that rapsyn is required for association of the AChR with utrophin and beta-dystroglycan, and for the agrin-induced increase in association with MuSK, but not for constitutive interactions with MuSK and src-related kinases. In rapsyn -/- myotubes, agrin caused normal tyrosine phosphorylation of AChR-associated and total MuSK, whereas phosphorylation of the AChR beta subunit, both constitutive and agrin-induced, was strongly reduced. These results show first that aneural myotubes contain preassembled AChR protein complexes that may function in the assembly of the postsynaptic apparatus, and second that rapsyn, in addition to its role in AChR phosphorylation, mediates selected protein interactions with the AChR and serves as a link between the AChR and the dystrophin/utrophin glycoprotein complex.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Brain Research Institute|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Date:||1 August 1999|
|Deposited On:||11 Feb 2008 12:12|
|Last Modified:||05 Apr 2016 12:12|
|Publisher:||Society for Neuroscience|
|Additional Information:||Holder of copyright: The Society for Neuroscience|
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