ArticleNature communications2024
Structure and function of Semaphorin-5A glycosaminoglycan interactions.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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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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.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin.Science advances · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- A long-chain heparan sulfate capture mechanism directs paracrine GDNF-GFRα1 signalling through RET.bioRxiv : the preprint server for biology · 2026Article
- Autism spectrum disorder-associated Sema5A p.Arg676Cys drives Arf6/FE65 signaling and aberrant cell morphogenesis.Scientific reports · 2026Article
- Diverse and location-specific roles of PlexinA2, PlexinA4, and NCAM in developing hippocampal mossy fibers.Translational psychiatry · 2026Article
- Identification and Mechanisms of Osteocyte Subsets Involved in the Pathological Progression of Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- The ErbB2-Dock7 Signaling Axis Mediates Excessive Cell Morphogenesis Induced by Autism Spectrum Disorder- and Intellectual Disability-Associated Sema5A p.Arg676Cys.International journal of molecular sciences · 2025Article
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- Expanding ligand-receptor interaction networks for axon guidance: Structural insights into signal crosstalk and specificity.Current opinion in neurobiology · 2025Review
- Compositional and topological determinants of a physiological Ashwell-Morell receptor ligand.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties.International journal of molecular sciences · 2025Review
- Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.Protein science : a publication of the Protein Society · 2025Article
- The network structural entropy for single-cell RNA sequencing data during skin aging.Briefings in bioinformatics · 2024Article
- AFrontiers in cellular and infection microbiology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important for GAG binding, however the underlying molecular basis and functions in vivo remain enigmatic. Here we dissect the structural basis for Sema5A:GAG specificity and demonstrate the functional significance of this interaction in vivo. Using x-ray crystallography, we reveal a dimeric fold variation for TSR4 that accommodates GAG interactions. TSR4 co-crystal structures identify binding residues validated by site-directed mutagenesis. In vitro and cell-based assays uncover specific GAG epitopes necessary for TSR association. We demonstrate that HS-GAG binding is preferred over CS-GAG and mediates Sema5A oligomerization. In vivo, Sema5A:GAG interactions are necessary for Sema5A function and regulate Plexin-A2 dependent dentate progenitor cell migration. Our study rationalizes Sema5A associated developmental and neurological disorders and provides mechanistic insights into how multifaceted guidance functions of a single transmembrane cue are regulated by proteoglycans.
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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.