ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Regulation of synaptic extracellular matrix composition is critical for proper synapse morphology.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Basement membrane patterning by spatial deployment of a secretion-regulating protease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interplay between MIG-6/papilin and TGF-β signaling promotes extracellular matrix remodeling and modulates the maintenance of neuronal architecture.bioRxiv : the preprint server for biology · 2025Article
- Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture.Research square · 2025Article
- Secreted Amyloid Precursor Protein Alpha (sAPPα) Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes.International journal of molecular sciences · 2023Article
- Extracellular matrix composition affects outgrowth of dendrites and dendritic spines on cortical neurons.Frontiers in cellular neuroscience · 2023Article
- Article
- Post-synaptic specialization of the neuromuscular junction: junctional folds formation, function, and disorders.Cell & bioscience · 2022Review
- Secreted Amyloid Precursor Protein Alpha, a Neuroprotective Protein in the Brain Has Widespread Effects on the Transcriptome and Proteome of Human Inducible Pluripotent Stem Cell-Derived Glutamatergic Neurons Related to Memory Mechanisms.Frontiers in neuroscience · 2022Article
- The MeshCODE to scale-visualising synaptic binary information.Frontiers in cellular neuroscience · 2022Article
- The HSPG syndecan is a core organizer of cholinergic synapses.The Journal of cell biology · 2021Article
- Blood-brain barrier dysfunction as a potential therapeutic target for neurodegenerative disorders.Archives of pharmacal research · 2021Review
- The Mechanical Basis of Memory - the MeshCODE Theory.Frontiers in molecular neuroscience · 2021Article
- A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth ineLife · 2020Article
- Article
- Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans.PloS one · 2020Article
- The Role of Tissue Inhibitors of Metalloproteinases in Organ Development and Regulation of ADAMTS Family Metalloproteinases inGenetics · 2019Article
- Wnts Promote Synaptic Assembly Through T-Cell Specific Transcription Factors inFrontiers in molecular neuroscience · 2018Article
- Secreted tissue inhibitor of matrix metalloproteinase restrictsJournal of cell science · 2017Article
- Evolution, immunity and the emergence of brain superautoantigens.F1000Research · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Synapses are surrounded by a layer of extracellular matrix (ECM), which is instrumental for their development and maintenance. ECM composition is dynamically controlled by proteases, but how the precise composition of the ECM affects synaptic morphology is largely unknown. Through an unbiased forward genetic screen, we found that Caenorhabditis elegans gon-1, a conserved extracellular ADAMTS protease, is required for maintaining proper synaptic morphology at the neuromuscular junction. In gon-1 mutants, once synapse formation is complete, motor neuron presynaptic varicosities develop into large bulbous protrusions that contain synaptic vesicles and active zone proteins. A concomitant overgrowth of postsynaptic muscle membrane is found in close apposition to presynaptic axonal protrusions. Mutations in the muscle-specific, actin-severing protein cofilin (unc-60) suppress the axon phenotype, suggesting that muscle outgrowth is necessary for presynaptic protrusions. gon-1 mutants can also be suppressed by loss of the ECM components collagen IV (EMB-9) and fibulin (FBL-1). We propose that GON-1 regulates a developmental switch out of an initial "pro-growth" phase during which muscle arms grow out and form synapses with motor neuron axons. We postulate that this switch involves degradation or reorganization of collagen IV (EMB-9), whereas FBL-1 opposes GON-1 by stabilizing EMB-9. Our results describe a mechanism for regulating synaptic ECM composition and reveal the importance of precise ECM composition for neuronal morphology and synapse integrity.
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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.