The function of p120 catenin in filopodial growth and synaptic vesicle clustering in neurons.
At the developing neuromuscular junction (NMJ), physical contact between motor axons and muscle cells initiates presynaptic and postsynaptic differentiation. Using Xenopus nerve-muscle cocultures, we previously showed that innervating axons induced muscle filopodia (myopodia), which facilitated interactions between the synaptic partners and promoted NMJ formation. The myopodia were generated by nerve-released signals through muscle p120 catenin (p120ctn), a protein of the cadherin complex that modulates the activity of Rho GTPases. Because axons also extend filopodia that mediate early nerve-muscle interactions, here we test p120ctn's function in the assembly of these presynaptic processes. Overexpression of wild-type p120ctn in Xenopus spinal neurons leads to an increase in filopodial growth and synaptic vesicle (SV) clustering along axons, whereas the development of these specializations is inhibited following the expression of a p120ctn mutant lacking sequences important for regulating Rho GTPases. The p120ctn mutant also inhibits the induction of axonal filopodia and SV clusters by basic fibroblast growth factor, a muscle-derived molecule that triggers presynaptic differentiation. Of importance, introduction of the p120ctn mutant into neurons hinders NMJ formation, which is observed as a reduction in the accumulation of acetylcholine receptors at innervation sites in muscle. Our results suggest that p120ctn signaling in motor neurons promotes nerve-muscle interaction and NMJ assembly.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Cheng
C
Chen
Pan P
PP
Li
Raghavan
R
Madhavan
H Benjamin
HB
Peng
D000818:Animals; D001369:Axons / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis; D020729:p120 GTPase Activating Protein / Q000235:genetics / Q000378:metabolism*
D051177:Catenins; D011950:Receptors, Cholinergic; D020729:p120 GTPase Activating Protein; D016222:Fibroblast Growth Factor 2