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Publication : Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold.

First Author  Apel ED Year  1997
Journal  Neuron Volume  18
Issue  4 Pages  623-35
PubMed ID  9136771 Mgi Jnum  J:111100
Mgi Id  MGI:3653016 Doi  10.1016/s0896-6273(00)80303-7
Citation  Apel ED, et al. (1997) Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold. Neuron 18(4):623-35
abstractText  Agrin-induced clustering of acetylcholine receptors (AChRs) in the postsynaptic membrane is a key step in synaptogenesis at the neuromuscular junction. The receptor tyrosine kinase MuSK is a component of the agrin receptor, while the cytoplasmic protein rapsyn is necessary for the clustering of AChRs and all other postsynaptic membrane components studied to date. We show here that MuSK remains concentrated at synaptic sites in rapsyn-deficient mutant mice, suggesting that MuSK forms a primary structural scaffold to which rapsyn attaches other synaptic components. Using nonmuscle cells, we show that rapsyn-MuSK interactions are mediated by the ectodomain of MuSK, suggesting the existence of a transmembrane intermediate. In addition to rapsyn's structural role, we demonstrate that it is required for an early step in MuSK signaling, AChR phosphorylation. This signaling requires the kinase domain of MuSK, but not its ectodomain. Thus, MuSK may interact with rapsyn in multiple ways to play both structural and signaling roles in agrin-induced differentiation.
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