ArticleDevelopment (Cambridge, England)2016
Two classes of matrix metalloproteinases reciprocally regulate synaptogenesis.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 45 citations in OpenAlex.
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- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Neuron-to-glia and glia-to-glia signaling directs critical period experience-dependent synapse pruning.Frontiers in cell and developmental biology · 2025Review
- Enhanced Age-Dependent Motor Impairment in Males ofBiology · 2024Article
- PTPN11/Corkscrew Activates Local Presynaptic Mapk Signaling to Regulate Synapsin, Synaptic Vesicle Pools, and Neurotransmission Strength, with a Dual Requirement in Neurons and Glia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Growth anisotropy of the extracellular matrix shapes a developing organ.Nature communications · 2023Article
- FMRP activity and control of Csw/SHP2 translation regulate MAPK-dependent synaptic transmission.PLoS biology · 2023Article
- Delta/Notch signaling in glia maintains motor nerve barrier function and synaptic transmission by controlling matrix metalloproteinase expression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Junctional instability in neuroepithelium and network hyperexcitability in a focal cortical dysplasia human model.Brain : a journal of neurology · 2022Article
- Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome.Frontiers in cell and developmental biology · 2022Review
- Secreted C-type lectin regulation of neuromuscular junction synaptic vesicle dynamics modulates coordinated movement.Journal of cell science · 2021Article
- Terminal Schwann Cell Aging: Implications for Age-Associated Neuromuscular Dysfunction.Aging and disease · 2021Review
- Roles of the synaptic molecules Hevin and SPARC in mouse neuromuscular junction development and repair.Neuroscience letters · 2021Article
- Glypicans and Heparan Sulfate in Synaptic Development, Neural Plasticity, and Neurological Disorders.Frontiers in neural circuits · 2021Review
- Cell-to-cell communication mediates glioblastoma progression inBiology open · 2020Article
- Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrateJournal of cell science · 2020Review
- Synapse development and maturation at the drosophila neuromuscular junction.Neural development · 2020Review
- Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue.Nature communications · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptogenesis requires orchestrated intercellular communication between synaptic partners, with trans-synaptic signals necessarily traversing the extracellular synaptomatrix separating presynaptic and postsynaptic cells. Extracellular matrix metalloproteinases (Mmps) regulated by secreted tissue inhibitors of metalloproteinases (Timps), cleave secreted and membrane-associated targets to sculpt the extracellular environment and modulate intercellular signaling. Here, we test the roles of Mmp at the neuromuscular junction (NMJ) model synapse in the reductionist Drosophila system, which contains just two Mmps (secreted Mmp1 and GPI-anchored Mmp2) and one secreted Timp. We found that all three matrix metalloproteome components co-dependently localize in the synaptomatrix and show that both Mmp1 and Mmp2 independently restrict synapse morphogenesis and functional differentiation. Surprisingly, either dual knockdown or simultaneous inhibition of the two Mmp classes together restores normal synapse development, identifying a reciprocal suppression mechanism. The two Mmp classes co-regulate a Wnt trans-synaptic signaling pathway modulating structural and functional synaptogenesis, including the GPI-anchored heparan sulfate proteoglycan (HSPG) Wnt co-receptor Dally-like protein (Dlp), cognate receptor Frizzled-2 (Frz2) and Wingless (Wg) ligand. Loss of either Mmp1 or Mmp2 reciprocally misregulates Dlp at the synapse, with normal signaling restored by co-removal of both Mmp classes. Correcting Wnt co-receptor Dlp levels in both Mmp mutants prevents structural and functional synaptogenic defects. Taken together, these results identify an Mmp mechanism that fine-tunes HSPG co-receptor function to modulate Wnt signaling to coordinate synapse structural and functional development.
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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.