ArticleProceedings of the National Academy of Sciences of the United States of America2013
MDGAs interact selectively with neuroligin-2 but not other neuroligins to regulate inhibitory synapse development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis.The Lancet. Neurology · 2017Pooled it
- Genomic Copy Number Variants Associated With Strabismus and Amblyopia in the All of Us Research Program.Investigative ophthalmology & visual science · 2026Article
- Distinct nanoscale architectures of GABAergic inhibitory synapses predict diverse synaptic output.bioRxiv : the preprint server for biology · 2026Article
- Molecular continuity between axon guidance and synaptic function.Molecules and cells · 2026Review
- Bazedoxifene reverses sexually dimorphic autistic-like abnormalities in biallelic MDGA1-mutant mice.EMBO molecular medicine · 2026Article
- Autism-associated ARHGEF9 variants impair GABAergic synapses and ultrasonic communication by reducing gephyrin phosphorylation.Molecular psychiatry · 2026Article
- Localization and Functional Characterization of MDGA1 in Mouse Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- An Integrative Framework Identifies Cooperative Targeting of Host Pathways by Tick Salivary miRNAs.Computational and structural biotechnology journal · 2026Article
- Necl-4/CADM4 regulates GABAergic synaptic strength on GABAergic inhibitory neurons via ErbB4 activation and prevents neuronal impairments.Molecular neurobiology · 2025Article
- Association between methylation quantitative trait loci and colorectal cancer risk, survival and cancer recurrence.British journal of cancer · 2025Article
- Article
- EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2.Progress in neurobiology · 2025Article
- Single-Cell Transcriptomic Profiling Reveals Regional Differences in the Prefrontal and Entorhinal Cortex of Alzheimer's Disease Brain.International journal of molecular sciences · 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
- Establishing a Mouse Model of NL3R617W-Associated Autism Spectrum Disorder for a Functional Study.Actas espanolas de psiquiatria · 2025Article
- Chronic stress induces depression through MDGA1-Neuroligin2 mediated suppression of inhibitory synapses in the lateral habenula.Theranostics · 2025Article
- RPS23RG1 inhibits SORT1-mediated lysosomal degradation of MDGA2 to protect against autism.Theranostics · 2025Article
- 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
- Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1.Nature neuroscience · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The MAM domain-containing GPI anchor proteins MDGA1 and MDGA2 are Ig superfamily adhesion molecules composed of six IG domains, a fibronectin III domain, a MAM domain, and a GPI anchor. MDGAs contribute to the radial migration and positioning of a subset of cortical neurons during early neural development. However, MDGAs continue to be expressed in postnatal brain, and their functions during postnatal neural development remain unknown. Here, we demonstrate that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. We observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. Importantly, RNAi-mediated knockdown of MDGAs increased the abundance of inhibitory but not excitatory synapses in a neuroligin-2-dependent manner. Conversely, overexpression of MDGA1 decreased the numbers of functional inhibitory synapses. Likewise, coexpression of both MDGA1 and neuroligin-2 reduced the synaptogenic capacity of neuroligin-2 in an artificial synapse-formation assay by abolishing the ability of neuroligin-2 to form an adhesion complex with neurexins. Taken together, our data suggest that MDGAs inhibit the activity of neuroligin-2 in controlling the function of inhibitory synapses and that MDGAs do so by binding to neuroligin-2.
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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.