Motor neurite outgrowth is selectively inhibited by cell surface MuSK and agrin.
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.
Dimitropoulou
Anastasia
A
Neuroscience Program, University of Miami School of Medicine, Miami, FL 33136, USA.
Bixby
John L
JL
D018171:Agrin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016466:CHO Cells; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D006224:Cricetinae; D015536:Down-Regulation / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D041681:NIH 3T3 Cells; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism
D018171:Agrin; D000906:Antibodies; D006131:Growth Inhibitors; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases