TY - JOUR
T1 - Rapsyn clusters and activates the synapse-specific receptor tyrosine kinase MuSK
AU - Gillespie, Susan K.H.
AU - Balasubramanian, Sudha
AU - Fung, Eric T.
AU - Huganir, Richard L.
N1 - Funding Information:
Correspondence should be addressed to R. L. H. We gratefully acknowledge Charles Jennings and Steve Burden for the gift of the tMuSK clone and Moses Chao for the TrkA receptor expression vector. We thank Stan Froehner for the 1234A and 88b MAbs and David Ginty for the TrkA antibody. Joe Steinbach kindly provided the QF-18 cell line. We especially thank Carol Doherty and Jeff Bernhardt for excellent technical assistance and Cindy Finch for secretarial support. This work was funded by the National Institutes of Health (NS24418) and the Muscular Dystrophy Association.
PY - 1996/5
Y1 - 1996/5
N2 - Nerve-induced clustering of the nicotinic acetylcholine receptor (AChR) requires rapsyn, a synaptic peripheral membrane protein, as well as protein- tyrosine kinase activity. Here, we show that rapsyn induces the clustering of the synapse-specific receptor-tyrosine kinase MuSK in transfected QT-6 fibroblasts. Furthermore, rapsyn stimulates the autophosphorylation of MUSK, leading to a subsequent MuSK-dependent increase in cellular tyrosine phosphorylation. Moreover, rapsyn-activated MuSK specifically phosphorylated the AChR β subunit, the same subunit that is tyrosine phosphorylated during innervation or agrin treatment of muscle. These results suggest rapsyn may mediate the synaptic localization of MuSK in muscle and that MuSK may play an important role in the agrin-induced clustering of the AChR.
AB - Nerve-induced clustering of the nicotinic acetylcholine receptor (AChR) requires rapsyn, a synaptic peripheral membrane protein, as well as protein- tyrosine kinase activity. Here, we show that rapsyn induces the clustering of the synapse-specific receptor-tyrosine kinase MuSK in transfected QT-6 fibroblasts. Furthermore, rapsyn stimulates the autophosphorylation of MUSK, leading to a subsequent MuSK-dependent increase in cellular tyrosine phosphorylation. Moreover, rapsyn-activated MuSK specifically phosphorylated the AChR β subunit, the same subunit that is tyrosine phosphorylated during innervation or agrin treatment of muscle. These results suggest rapsyn may mediate the synaptic localization of MuSK in muscle and that MuSK may play an important role in the agrin-induced clustering of the AChR.
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U2 - 10.1016/S0896-6273(00)80118-X
DO - 10.1016/S0896-6273(00)80118-X
M3 - Article
C2 - 8630253
AN - SCOPUS:0029982641
SN - 0896-6273
VL - 16
SP - 953
EP - 962
JO - Neuron
JF - Neuron
IS - 5
ER -