ArticleNeuron2017
Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges.
Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- Topological modeling of gene expression in the brain with Huntington's disease reveals selective disruption of co-expression network.Scientific reports · 2026Article
- Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases.Communications biology · 2026Review
- Weaker neuroligin 2-neurexin β1 interaction tethers membranes and recruits gephyrin at membrane junctions through clustering.Science advances · 2026Article
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- High-content image-based pooled screens reveal regulators of synaptogenesis.Cell reports · 2025Article
- EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2.Progress in neurobiology · 2025Article
- Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.PLoS biology · 2025Article
- Chronic stress induces depression through MDGA1-Neuroligin2 mediated suppression of inhibitory synapses in the lateral habenula.Theranostics · 2025Article
- RLS-associated MEIS transcription factors control distinct processes in human neural stem cells.Scientific reports · 2024Article
- Continuous cell type diversification throughout the embryonic and postnatal mouse visual cortex development.bioRxiv : the preprint server for biology · 2024Article
- Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABACommunications biology · 2024Article
- Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine.International journal of molecular sciences · 2024Article
- MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior.Neuroscience bulletin · 2024Article
- MDGAs perform activity-dependent synapse type-specific suppression via distinct extracellular mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice.Molecular autism · 2024Article
- Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.The Journal of biological chemistry · 2023Article
- RNAseq Analysis of FABP4 Knockout Mouse Hippocampal Transcriptome Suggests a Role for WNT/β-Catenin in Preventing Obesity-Induced Cognitive Impairment.International journal of molecular sciences · 2023Article
- Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins.Journal of translational medicine · 2022Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroligins and neurexins promote synapse development and validation by forming trans-synaptic bridges spanning the synaptic cleft. Select pairs promote excitatory and inhibitory synapses, with neuroligin 2 (NLGN2) limited to inhibitory synapses and neuroligin 1 (NLGN1) dominating at excitatory synapses. The cell-surface molecules, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) and 2 (MDGA2), regulate trans-synaptic adhesion between neurexins and neuroligins, impacting NLGN2 and NLGN1, respectively. We have determined the molecular mechanism of MDGA action. MDGA1 Ig1-Ig2 is sufficient to bind NLGN2 with nanomolar affinity; its crystal structure reveals an unusual locked rod-shaped array. In the crystal structure of the complex, two MDGA1 Ig1-Ig2 molecules each span the entire NLGN2 dimer. Site-directed mutagenesis confirms the observed interaction interface. Strikingly, Ig1 from MDGA1 binds to the same region on NLGN2 as neurexins do. Thus, MDGAs regulate the formation of neuroligin-neurexin trans-synaptic bridges by sterically blocking access of neurexins to neuroligins.
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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.