ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Semaphorin4D Induces Inhibitory Synapse Formation by Rapid Stabilization of Presynaptic Boutons via MET Coactivation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Coordinated Pre- and Postsynaptic Protein Dynamics Underlie Rapid Sema4D-Induced Inhibitory Synapse Assembly.eNeuro · 2026Article
- Coordinated pre- and postsynaptic protein dynamics underlie rapid Sema4D-mediated inhibitory synapse assembly.bioRxiv : the preprint server for biology · 2026Article
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- Plexin-B1 and Plexin-B2 play non-redundant roles in GABAergic synapse formation.Molecular and cellular neurosciences · 2024Article
- Semaphorin 4D induced inhibitory synaptogenesis decreases epileptiform activity and alters progression to Status Epilepticus in mice.Epilepsy research · 2023Article
- Circuit-selective cell-autonomous regulation of inhibition in pyramidal neurons by Ste20-like kinase.Cell reports · 2022Article
- An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Axonal CB1 Receptors Mediate Inhibitory Bouton Formation via cAMP Increase and PKA.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins.International journal of molecular sciences · 2021Review
- Experience-Dependent Inhibitory Plasticity Is Mediated by CCK+ Basket Cells in the Developing Dentate Gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Amyloid-β Oligomers Induce Only Mild Changes to Inhibitory Bouton Dynamics.Journal of Alzheimer's disease reports · 2021Article
- Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses.Frontiers in molecular neuroscience · 2021Article
- The Role of Semaphorins in Metabolic Disorders.International journal of molecular sciences · 2020Review
- Reduction of Dendritic Inhibition in CA1 Pyramidal Neurons in Amyloidosis Models of Early Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2020Article
- Class 4 Semaphorins and Plexin-B receptors regulate GABAergic and glutamatergic synapse development in the mammalian hippocampus.Molecular and cellular neurosciences · 2018Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in inhibitory connections are essential for experience-dependent circuit adaptations. Defects in inhibitory synapses are linked to neurodevelopmental disorders, but the molecular processes underlying inhibitory synapse formation are not well understood. Here we use high-resolution two-photon microscopy in organotypic hippocampal slices from GAD65-GFP mice of both sexes to examine the signaling pathways induced by the postsynaptic signaling molecule Semaphorin4D (Sema4D) during inhibitory synapse formation. By monitoring changes in individual GFP-labeled presynaptic boutons, we found that the primary action of Sema4D is to induce stabilization of presynaptic boutons within tens of minutes. Stabilized boutons rapidly recruited synaptic vesicles, followed by accumulation of postsynaptic gephyrin and were functional after 24 h, as determined by electrophysiology and immunohistochemistry. Inhibitory boutons are only sensitive to Sema4D at a specific stage during synapse formation and sensitivity to Sema4D is regulated by network activity. We further examined the intracellular signaling cascade triggered by Sema4D and found that bouton stabilization occurs through rapid remodeling of the actin cytoskeleton. This could be mimicked by the actin-depolymerizing drug latrunculin B or by reducing ROCK activity. We discovered that the intracellular signaling cascade requires activation of the receptor tyrosine kinase MET, which is a well known autism risk factor. By using a viral approach to reduce MET levels specifically in inhibitory neurons, we found that their axons are no longer sensitive to Sema4D signaling. Together, our data yield important insights into the molecular pathway underlying activity-dependent Sema4D-induced synapse formation and reveal a novel role for presynaptic MET at inhibitory synapses.
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