title: Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells.
abstract: Cumulative evidence indicates that Wnt pathways play crucial and diverse roles to assemble the neuromuscular junction (NMJ), a peripheral synapse characterized by the clustering of acetylcholine receptors (AChR) on postsynaptic densities. The molecular determinants of Wnt effects at the NMJ are still to be fully elucidated. We report here that the Wnt receptor Frizzled-9 (Fzd9) is expressed in developing skeletal muscles during NMJ synaptogenesis. In cultured myotubes, gain- and loss-of-function experiments revealed that Fzd9-mediated signaling impairs the AChR-clustering activity of agrin, an organizer of postsynaptic differentiation. Overexpression of Fzd9 induced the cytosolic accumulation of β-catenin, a key regulator of Wnt signaling. Consistently, Fzd9 and β-catenin localize in the postsynaptic domain of embryonic NMJs in vivo. Our findings represent the first evidence pointing to a crucial role of a Fzd-mediated, β-catenin-dependent signaling on the assembly of the vertebrate NMJ.
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Evelyn C
authors.initials: EC
authors.lastname: Avilés
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hanna
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ojeda
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Pérez
authors.affiliation: Faculty of Biological Sciences, Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andres Bello Santiago, Chile.
authors.forename: Giancarlo V
authors.initials: GV
authors.lastname: De Ferrari
authors.affiliation: Department of Biomedicine, Universidad de Antofagasta Antofagasta, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zamorano
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Miguel
authors.initials: M
authors.lastname: Albistur
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sandoval
authors.affiliation: Laboratory of Developmental Neurobiology, Department of Cell Biology, Faculty of Biological Sciences, Millennium Nucleus of Regenerative Biology, Center for Advanced Microscopy, Universidad de Concepción Concepción, Chile.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Henríquez
keywords: Frizzled receptors; Wnt proteins; acetylcholine receptor; neuromuscular junction; postsynaptic; skeletal muscle