Resumen
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.
| Idioma original | English |
|---|---|
| Número de artículo | 110 |
| Publicación | Frontiers in Cellular Neuroscience |
| Volumen | 8 |
| N.º | 1 APR |
| DOI | |
| Estado | Published - 17 abr 2014 |
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ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
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Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells. / Avilés, Evelyn C.; Pinto, Cristina; Hanna, Patricia; Ojeda, Jorge; Pérez, Viviana; De Ferrari, Giancarlo V.; Zamorano, Pedro; Albistur, Miguel; Sandoval, Daniel; Henríquez, Juan P.
En: Frontiers in Cellular Neuroscience, Vol. 8, N.º 1 APR, 110, 17.04.2014.Resultado de la investigación: Article
TY - JOUR
T1 - Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells
AU - Avilés, Evelyn C.
AU - Pinto, Cristina
AU - Hanna, Patricia
AU - Ojeda, Jorge
AU - Pérez, Viviana
AU - De Ferrari, Giancarlo V.
AU - Zamorano, Pedro
AU - Albistur, Miguel
AU - Sandoval, Daniel
AU - Henríquez, Juan P.
PY - 2014/4/17
Y1 - 2014/4/17
N2 - 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.
AB - 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.
KW - Acetylcholine receptor
KW - Frizzled receptors
KW - Neuromuscular junction
KW - Postsynaptic
KW - Skeletal muscle
KW - Wnt proteins
UR - http://www.scopus.com/inward/record.url?scp=84898911176&partnerID=8YFLogxK
U2 - 10.3389/fncel.2014.00110
DO - 10.3389/fncel.2014.00110
M3 - Article
AN - SCOPUS:84898911176
VL - 8
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
IS - 1 APR
M1 - 110
ER -