ArticleStructure (London, England : 1993)2021
Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges.
Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Teneurins Are SPARCL1 Receptors.bioRxiv : the preprint server for biology · 2026Article
- Life Cycle and Circadian Rhythms in Central Resident Immunity and Neuropsychiatric Pathology.Neuroscience bulletin · 2026Review
- Hevin/sparcl-1 as a potential biomarker and therapy in age-associated cognitive decline.Neural regeneration research · 2026Article
- Article
- Modular Platform for Rapidly Investigating Long-Distance Propagation of Human Neural Network Activity.Advanced healthcare materials · 2026Article
- Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.Frontiers in synaptic neuroscience · 2026Review
- Multifaceted Astrocyte-Neuron Cross-Talk in Neuropathic Pain: Potential Mechanisms and Functional Implications.Journal of pain research · 2026Review
- Astrocytes Control Cocaine-Induced Synaptic Plasticity and Reward Through the Matricellular Protein Hevin.Biological psychiatry · 2025Article
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- Glioma-derived SPARCL1 promotes the formation of peritumoral neuron-glioma synapses.Journal of neuro-oncology · 2025Article
- Astrocyte Modulation of Synaptic Plasticity Mediated by Activity-Dependent Sonic Hedgehog Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Identification of candidate genes involved in Zika virus-induced reversible paralysis of mice.Scientific reports · 2025Article
- Alpha-neurexins in health and disease.Frontiers in molecular neuroscience · 2025Review
- Chronic stress induces depression through MDGA1-Neuroligin2 mediated suppression of inhibitory synapses in the lateral habenula.Theranostics · 2025Article
- GEARBOCS: An Adeno Associated Virus Tool forbioRxiv : the preprint server for biology · 2024Article
- New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity.Cell death discovery · 2024Review
- Efficient Escorting Strategy for Aggregation-Prone Notch EGF Repeats with Sparcl1.Molecules (Basel, Switzerland) · 2024Article
- Mutations in Hevin/Sparcl1 and risk of autism spectrum disorder.Neural regeneration research · 2023Article
- Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.The Journal of biological chemistry · 2023Article
- Long-term plasticity of astrocytic phenotypes and their control by neurons in health and disease.Essays in biochemistry · 2023Review
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4 authors.
Funding
Abstract
Hevin is secreted by astrocytes and its synaptogenic effects are antagonized by the related protein, SPARC. Hevin stabilizes neurexin-neuroligin transsynaptic bridges in vivo. A third protein, membrane-tethered MDGA, blocks these bridges. Here, we reveal the molecular underpinnings of a regulatory network formed by this trio of proteins. The hevin FS-EC structure differs from SPARC, in that the EC domain appears rearranged around a conserved core. The FS domain is structurally conserved and it houses nanomolar affinity binding sites for neurexin and neuroligin. SPARC also binds neurexin and neuroligin, competing with hevin, so its antagonist action is rooted in its shortened N-terminal region. Strikingly, the hevin FS domain competes with MDGA for an overlapping binding site on neuroligin, while the hevin EC domain binds the extracellular matrix protein collagen (like SPARC), so that this trio of proteins can regulate neurexin-neuroligin transsynaptic bridges and also extracellular matrix interactions, impacting synapse formation and ultimately neural circuits.
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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.