TY - JOUR
T1 - Motor neurite outgrowth is selectively inhibited by cell surface MuSK and agrin
AU - Dimitropoulou, Anastasia
AU - Bixby, John L.
N1 - Funding Information:
We thank Dr. Markus Ruegg for his generous gift of numerous useful reagents, his insightful comments on the design of some of the experiments, and his thoughtful critique of the manuscript. We thank Dr. Paul Martin for his generous gift of the CT antibodies, Dr. John Lowe for the CT acetyltransferase construct, and Dr. Pedro Beltran for technical advice and intellectual support. This work was supported by grants to JLB from the NIH (NS38920) and the NSF (IBN9603928).
PY - 2005/2
Y1 - 2005/2
N2 - During neuromuscular development, "stop signals" present on the target myotube inhibit motor axon growth. Mice lacking either the neuronal form of agrin or the muscle-specific tyrosine kinase (MuSK) lose stop signal activity, suggesting that they are part of such signals or induce them in myotubes. To test whether MuSK complexes form stop signals in the absence of myotube signaling, we cultured ciliary ganglion (CG) neurons with nonmuscle cells expressing cell-surface MuSK. Expression of MuSK had no effect on neuronal adhesion. MuSK expression, however, inhibited neurite outgrowth from CG neurons, but not retinal ganglion cell neurons. The neurite-inhibitory effect could be completely reversed by an antibody to the MuSK extracellular domain, and partially reversed by an antibody to agrin, suggesting that inhibition is mediated by a complex of these proteins. Thus, an agrin/MuSK complex may form part of a motor neuron stop signal involved in "reverse signaling" to the motor neuron.
AB - During neuromuscular development, "stop signals" present on the target myotube inhibit motor axon growth. Mice lacking either the neuronal form of agrin or the muscle-specific tyrosine kinase (MuSK) lose stop signal activity, suggesting that they are part of such signals or induce them in myotubes. To test whether MuSK complexes form stop signals in the absence of myotube signaling, we cultured ciliary ganglion (CG) neurons with nonmuscle cells expressing cell-surface MuSK. Expression of MuSK had no effect on neuronal adhesion. MuSK expression, however, inhibited neurite outgrowth from CG neurons, but not retinal ganglion cell neurons. The neurite-inhibitory effect could be completely reversed by an antibody to the MuSK extracellular domain, and partially reversed by an antibody to agrin, suggesting that inhibition is mediated by a complex of these proteins. Thus, an agrin/MuSK complex may form part of a motor neuron stop signal involved in "reverse signaling" to the motor neuron.
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U2 - 10.1016/j.mcn.2004.09.013
DO - 10.1016/j.mcn.2004.09.013
M3 - Article
C2 - 15691710
AN - SCOPUS:13444282201
VL - 28
SP - 292
EP - 302
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
SN - 1044-7431
IS - 2
ER -