ArticlePLoS genetics2012
A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 82 citations in OpenAlex.
- Complex anionic and zwitterionic N-glycans in Drosophila melanogaster.Biochimica et biophysica acta. General subjects · 2026Article
- A synthetic HS structure selectively impairs the morphology and function of excitatory synapse by disrupting neurexin1 interactions.Glycobiology · 2025Article
- Loss of the extracellular matrix protein Perlecan disrupts axonal and synaptic stability duringeLife · 2023Article
- Regulation of morphogen pathways by a Drosophila chondroitin sulfate proteoglycan Windpipe.Journal of cell science · 2023Article
- Article
- Recovery of Post-Stroke Spatial Memory and Thalamocortical Connectivity Following Novel Glycomimetic and rhBDNF Treatment.International journal of molecular sciences · 2022Article
- Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome.Frontiers in cell and developmental biology · 2022Review
- Article
- The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair.International journal of molecular sciences · 2021Review
- Secreted C-type lectin regulation of neuromuscular junction synaptic vesicle dynamics modulates coordinated movement.Journal of cell science · 2021Article
- Expression of Heparan Sulfate Endosulfatases in the Adult Mouse Brain: Co-expression ofFrontiers in neuroanatomy · 2021Article
- Glypicans and Heparan Sulfate in Synaptic Development, Neural Plasticity, and Neurological Disorders.Frontiers in neural circuits · 2021Review
- 3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro.Scientific reports · 2020Article
- Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrateJournal of cell science · 2020Review
- Genetic background mutations drive neural circuit hyperconnectivity in a fragile X syndrome model.BMC biology · 2020Article
- Functional analysis of glycosylation using Drosophila melanogaster.Glycoconjugate journal · 2020Review
- Heparan sulfate negatively regulates intestinal stem cell proliferation inBiology open · 2019Article
- BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.Nature communications · 2019Article
- Roles of glycosaminoglycans as regulators of ligand/receptor complexes.Open biology · 2018Review
- Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A Drosophila transgenic RNAi screen targeting the glycan genome, including all N/O/GAG-glycan biosynthesis/modification enzymes and glycan-binding lectins, was conducted to discover novel glycan functions in synaptogenesis. As proof-of-product, we characterized functionally paired heparan sulfate (HS) 6-O-sulfotransferase (hs6st) and sulfatase (sulf1), which bidirectionally control HS proteoglycan (HSPG) sulfation. RNAi knockdown of hs6st and sulf1 causes opposite effects on functional synapse development, with decreased (hs6st) and increased (sulf1) neurotransmission strength confirmed in null mutants. HSPG co-receptors for WNT and BMP intercellular signaling, Dally-like Protein and Syndecan, are differentially misregulated in the synaptomatrix of these mutants. Consistently, hs6st and sulf1 nulls differentially elevate both WNT (Wingless; Wg) and BMP (Glass Bottom Boat; Gbb) ligand abundance in the synaptomatrix. Anterograde Wg signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb signaling via synaptic MAD phosphorylation and nuclear import are differentially activated in hs6st and sulf1 mutants. Consequently, transcriptional control of presynaptic glutamate release machinery and postsynaptic glutamate receptors is bidirectionally altered in hs6st and sulf1 mutants, explaining the bidirectional change in synaptic functional strength. Genetic correction of the altered WNT/BMP signaling restores normal synaptic development in both mutant conditions, proving that altered trans-synaptic signaling causes functional differentiation defects.
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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.