ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction

Sigoillot, Séverine M.; Bourgeois, Francine; Lambergeon, Monique; Strochlic, Laure; Legay, Claire

doi:10.1523/jneurosci.4374-09.2010

Cited by 66 publications

(107 citation statements)

References 60 publications

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“…However, binding of ColQ to MuSK is dispensable for clustering ColQ in humans, but is required for facilitating AChR clustering. 32 Second, AChE could be deficient in severely affected muscles but not in the biopsied intercostal muscles. However, the respiratory functions of the patients who had intercostal muscle biopsies were severely compromised.…”

Section: In Vitro Plate-binding Assay Shows That Musk-igg Blocks Bindmentioning

confidence: 98%

“…In myotubes of ColqϪ/Ϫ mice, the number of membrane-bound MuSK is prominently reduced, and agrin-mediated phosphorylation of the AChR ␤ subunit and the subsequent clustering of AChR are reduced to 30%-50% of the wild type. 32 Thus, compromised clustering of AChRs at the NMJs in some MuSK-MG patients could result from blocking of ColQ binding to MuSK but not from blocking of LRP4 binding to MuSK.…”

Section: In Vitro Plate-binding Assay Shows That Musk-igg Blocks Bindmentioning

confidence: 99%

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Anti-MuSK autoantibodies block binding of collagen Q to MuSK

Kawakami¹,

Ito²,

Hirayama³

et al. 2011

Neurology

112

125

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Objective: Muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) accounts for 5%-15% of autoimmune MG. MuSK mediates the agrin-signaling pathway and also anchors the collagenic tail subunit (ColQ) of acetylcholinesterase (AChE). The exact molecular target of MuSK-immunoglobulin G (IgG), however, remains elusive. As acetylcholine receptor (AChR) deficiency is typically mild and as cholinesterase inhibitors are generally ineffective, we asked if MuSK-IgG interferes with binding of ColQ to MuSK. Methods:We used 3 assays: in vitro overlay of the human ColQ-tailed AChE to muscle sections of ColqϪ/Ϫ mice; in vitro plate-binding assay to quantitate binding of MuSK to ColQ and to LRP4; and passive transfer of MuSK-IgG to mice.

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Section: In Vitro Plate-binding Assay Shows That Musk-igg Blocks Bindmentioning

confidence: 98%

Section: In Vitro Plate-binding Assay Shows That Musk-igg Blocks Bindmentioning

confidence: 99%

Anti-MuSK autoantibodies block binding of collagen Q to MuSK

Kawakami¹,

Ito²,

Hirayama³

et al. 2011

Neurology

112

125

View full text Add to dashboard Cite

show abstract

“…We used a mouse muscle cell line generated in our laboratory that carries a temperature-sensitive large T oncogene. Stages of muscle differentiation have been described previously (see Materials and Methods;Cartaud et al, 2004;Sigoillot et al, 2010Sigoillot et al, , 2016. We quantified Wnt11 mRNA expression by RT-PCR at three muscle cell stages.…”

Section: Wnt4 and Wnt11 Cooperatively Enhance Achr Clusteringmentioning

confidence: 99%

“…The MLCL polyclonal muscle cell line was generated in our laboratory from H-2Kb-tsA58 newborn mouse muscle and was cultured as described previously (Cartaud et al, 2004;Sigoillot et al, 2010Sigoillot et al, , 2016. Three stages of muscle cell differentiation were selected for analysis: T1, when cells are mostly myotubes (day 0); T2 (day 2), when AChR clusters are visualized; and T3 (day 5), when both AChR and AChE clusters are observed (Guerra et al, 2005).…”

Section: Immunoprecipitation and Western Blotmentioning

confidence: 99%

Wnts contribute to neuromuscular junction formation through distinct signaling pathways

et al. 2017

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Understanding the developmental steps that shape formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers is crucial. Wnt morphogens are key players in the formation of this specialized peripheral synapse, but their individual and collaborative functions and downstream pathways remain poorly understood at the NMJ. Here, we demonstrate through Wnt4 and Wnt11 gain-of-function studies in cell culture or in mice that Wnts enhance acetylcholine receptor (AChR) clustering and motor axon outgrowth. By contrast, loss of Wnt11 or Wnt-dependent signaling in vivo decreases AChR clustering and motor nerve terminal branching. Both Wnt4 and Wnt11 stimulate AChR mRNA levels and AChR clustering downstream of activation of the β-catenin pathway. Strikingly, Wnt4 and Wnt11 co-immunoprecipitate with Vangl2, a core component of the planar cell polarity (PCP) pathway, which accumulates at embryonic NMJs. Moreover, mice bearing a Vangl2 loss-of-function mutation (loop-tail) exhibit fewer AChR clusters and overgrowth of motor axons bypassing AChR clusters. Together, our results provide genetic and biochemical evidence that Wnt4 and Wnt11 cooperatively contribute to mammalian NMJ formation through activation of both the canonical and Vangl2-dependent core PCP pathways.

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“…2005; Sigoillot et al . 2010). This association may explain reduced expression of α ‐dystroglycan observed in some cats (Martin et al .…”

mentioning

confidence: 99%

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy

et al. 2015

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SummarySome Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS). A genome‐wide association study and whole‐genome sequencing suggested a causal variant for this entity was a c.1190G>A variant causing a cysteine to tyrosine substitution (p.Cys397Tyr) within the C‐terminal domain of collagen‐like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). Alpha‐dystroglycan expression, which is associated with COLQ anchorage at the motor end‐plate, has been shown to be deficient in affected cats. Eighteen affected cats were identified by genotyping, including cats from the original clinical descriptions in 1993 and subsequent publications. Eight Devon Rex and one Sphynx not associated with the study were identified as carriers, suggesting an allele frequency of ~2.0% in Devon Rex. Over 350 tested cats from other breeds did not have the variant. Characteristic clinical features and variant presence in all affected cats suggest a model for COLQ CMS. The association between the COLQ variant and this CMS affords clinicians the opportunity to confirm diagnosis via genetic testing and permits owners and breeders to identify carriers in the population. Moreover, accurate diagnosis increases available therapeutic options for affected cats based on an understanding of the pathophysiology and experience from human CMS associated with COLQ variants.

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ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction

Cited by 66 publications

References 60 publications

Anti-MuSK autoantibodies block binding of collagen Q to MuSK

Anti-MuSK autoantibodies block binding of collagen Q to MuSK

Wnts contribute to neuromuscular junction formation through distinct signaling pathways

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy

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