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Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells.

Front Cell Neurosci. 2014 Apr 17;8:110. doi:10.3389/fncel.2014.00110. eCollection 2014
Evelyn C Avilés 1 , Cristina Pinto 1 , Patricia Hanna 1 , Jorge Ojeda 1 , Viviana Pérez 1 , Giancarlo V De Ferrari 2 , Pedro Zamorano 3 , Miguel Albistur 1 , Daniel Sandoval 1 , Juan P Henríquez 1
Evelyn C Avilés 1 , Cristina Pinto 1 , Patricia Hanna 1 , Jorge Ojeda 1 , Viviana Pérez 1 , Giancarlo V De Ferrari 2 , Pedro Zamorano 3 , Miguel Albistur 1 , Daniel Sandoval 1 , Juan P Henríquez 1
+ et al

[No authors listed]

Author information
  • 1 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.
  • 2 Faculty of Biological Sciences, Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andres Bello Santiago, Chile.
  • 3 Department of Biomedicine, Universidad de Antofagasta Antofagasta, Chile.
全文

摘要


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.

KEYWORDS: Frizzled receptors, Wnt proteins, acetylcholine receptor, neuromuscular junction, postsynaptic, skeletal muscle