TY - JOUR
T1 - Rapsyn is required for MuSK signaling and recruits synaptic components to a musk-containing scaffold
AU - Apel, Elizabeth D.
AU - Glass, David J.
AU - Moscoso, Lisa M.
AU - Yancopoulos, George D.
AU - Sanes, Joshua R.
N1 - Funding Information:
Address correspondence to J. R. S., Department of Anatomy and Neurobiology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110. We thank Medha Gautam for advice; Sonal Shah for supplying some chimera constructs; and Jeannette Cunningham, David Gies, Mia Nichol, and Carol Candler for expert assistance. E. D. A. is a Fellow of the American Heart Association. This work was supported by grants from the National Institutes of Health.
PY - 1997/4
Y1 - 1997/4
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0030940161
U2 - 10.1016/S0896-6273(00)80303-7
DO - 10.1016/S0896-6273(00)80303-7
M3 - Article
C2 - 9136771
AN - SCOPUS:0030940161
SN - 0896-6273
VL - 18
SP - 623
EP - 635
JO - Neuron
JF - Neuron
IS - 4
ER -