ArticleCell & bioscience2021
Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Peripheral Nerve Injury and Denervation-Induced Sarcopenia with a Focus on Pharmacological Dual-Target Strategies.Biomolecules & therapeutics · 2026Review
- Simple molecules make difference: short peptides play a novel role in slowing senescence.npj aging · 2025Review
- Neddylation E1 Obligatory Subunit Nae1 Is Critical to Neuromuscular Junction Development and Maintenance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion.Cell & bioscience · 2023Article
- Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals.Nature communications · 2023Article
- Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling.Frontiers in immunology · 2023Article
- Article
- Motoneurons innervation determines the distinct gene expressions in multinucleated myofibers.Cell & bioscience · 2022Article
- Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease.Acta neuropathologica communications · 2022Article
- Knockdown of long noncoding RNA HUMT inhibits the proliferation and metastasis by regulating miR-455-5p/LRP4 axis in hepatocellular carcinoma.Bioengineered · 2022Article
- Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons.Biomolecules · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe neuromuscular junction (NMJ) is a peripheral synapse critical to muscle contraction. Like acetylcholine receptors (AChRs), many essential proteins of NMJ are extremely concentrated at the postjunctional membrane. However, the mechanisms of synapse-specific concentration are not well understood; furthermore, it is unclear whether signaling molecules critical to NMJ formation and maintenance are also locally transcribed.
resultsWe studied the β-gal activity encoded by a lacZ cassette driven by the promoter of the Lrp4 gene. As reported for Lrp4 mRNA, β-gal was in the central region in embryonic muscles and at the NMJ after its formation. However, β-gal was no longer in the central areas of muscle fibers in Lrp4 or MuSK mutant mice, indicating a requirement of Lrp4/MuSK signaling. This phenotype could be rescued by transgenic expression of LRP4 with a transmembrane domain but not soluble ECD in Lrp4 mutant mice. β-gal and AChR clusters were distributed in a broader region in lacZ/ECD than that of heterozygous lacZ/+ mice, indicating an important role of the transmembrane domain in Lrp4 signaling. Synaptic β-gal activity became diffused after denervation or treatment with µ-conotoxin, despite its mRNA was increased, indicating synaptic Lrp4 mRNA enrichment requires muscle activity. β-gal was also diffused in aged mice but became re-concentrated after muscle stimulation. Finally, Lrp4 mRNA was increased in C2C12 myotubes by Wnt ligands in a manner that could be inhibited by RKI-1447, an inhibitor of ROCK in Wnt non-canonical signaling. Injecting RKI-1447 into muscles of adult mice diminished Lrp4 synaptic expression.
conclusionsThis study demonstrates that synapse-specific enrichment of Lrp4 mRNA requires a coordinated interaction between Lrp4/MuSK signaling, muscle activity, and Wnt non-canonical signaling. Thus, the study provides a new mechanism for Lrp4 mRNA enrichment. It also provides a potential target for the treatment of NMJ aging and other NMJ-related diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.