Rapsyn clusters and activates the synapse-specific receptor tyrosine kinase MuSK.
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 beta 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.
Gillespie
S K
SK
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Balasubramanian
S
S
Fung
E T
ET
Huganir
R L
RL
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011784:Quail; D011940:Receptor Aggregation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D017931:DNA Primers; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C051609:peripheral membrane protein 43K; C095714:MUSK protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases