title: Involvement of p120 catenin in myopodial assembly and nerve-muscle synapse formation.
abstract: At developing neuromuscular junctions (NMJs), muscles initially contact motor axons by microprocesses, or myopodia, which are induced by nerves and nerve-secreted agrin, but it is unclear how myopodia are assembled and how they influence synaptic differentiation at the NMJ. Here, we report that treatment of cultured muscle cells with agrin transiently depleted p120 catenin (p120ctn) from cadherin junctions in situ, and increased the tyrosine phosphorylation and decreased the cadherin-association of p120ctn in cell extracts. Whereas ectopic expression of wild-type p120ctn in muscle generated myopodia in the absence of agrin, expression of a specific dominant-negative mutant form of p120ctn, which blocks filopodial assembly in nonmuscle cells, suppressed nerve- and agrin-induction of myopodia. Significantly, approaching neurites triggered reduced acetylcholine receptor (AChR) clustering along the edges of muscle cells expressing mutant p120ctn than of control cells, although the ability of the mutant cells to cluster AChRs was itself normal. Our results indicate a novel role of p120ctn in agrin-induced myopodial assembly and suggest that myopodia increase muscle-nerve contacts and muscle's access to neural agrin to promote NMJ formation.
authors.affiliation: Department of Biology, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Raghavan
authors.initials: R
authors.lastname: Madhavan
authors.forename: Xiaotao T
authors.initials: XT
authors.lastname: Zhao
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.forename: H Benjamin
authors.initials: HB
authors.lastname: Peng
mesh_terms: D018171:Agrin / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004625:Embryo, Nonmammalian; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D032342:Muscle Cells / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus; D000095002:Delta Catenin
chemical_list: D018171:Agrin; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D011950:Receptors, Cholinergic; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D000095002:Delta Catenin