ArticleProceedings of the National Academy of Sciences of the United States of America2015
The LGI1-ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 128 citations in OpenAlex.
- The AMPA receptor life cycle: assembly, regulation and synaptic diversity.Nature reviews. Neuroscience · 2026Review
- Pathological extracellular matrix changes in decellularized normal appearing gray matter and subpial multiple sclerosis lesions.iScience · 2026Article
- Impaired consolidation of spatial memory during sleep in patients with leucine-rich glioma-inactivated 1-associated limbic encephalitis.Brain communications · 2026Article
- Exploration of Canarium odontophyllum fruit phytoconstituents as potential candidates against epilepsy using in silico studies.Journal, genetic engineering & biotechnology · 2025Article
- Mechanism of DKK3 protecting brain tissues in ischemic stroke by regulating LGI1 expression and activity.European journal of medical research · 2025Article
- Structural insights into heterohexameric assembly of epilepsy-related ligand-receptor complex LGI1-ADAM22.eLife · 2025Article
- Efgartigimod treatment for therapy-refractory autoimmune encephalitis with coexistent NMDAR and LGI1 antibodies: a case report and literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.Brain, behavior, and immunity · 2025Article
- A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.Brain : a journal of neurology · 2025Article
- Development of Differential Sublaminar Feedforward Inhibitory Circuits in CA1 Hippocampus RequiresThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic KNeurology(R) neuroimmunology & neuroinflammation · 2024Article
- Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.Neuron · 2024Article
- Disrupted hypothalamic transcriptomics and proteomics in a mouse model of type 2 diabetes exposed to recurrent hypoglycaemia.Diabetologia · 2024Article
- Inactive metallopeptidase homologs: the secret lives of pseudopeptidases.Frontiers in molecular biosciences · 2024Review
- Rescue of Normal Excitability in LGI1-Deficient Epileptic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.bioRxiv : the preprint server for biology · 2023Article
- Imbalance of glutamatergic and GABAergic neurotransmission in audiogenic seizure-susceptible LHeliyon · 2023Article
- LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period.The Journal of cell biology · 2023Article
- A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating KCell & bioscience · 2023Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Synapse development is coordinated by a number of transmembrane and secreted proteins that come together to form synaptic organizing complexes. Whereas a variety of synaptogenic proteins have been characterized, much less is understood about the molecular networks that support the maintenance and functional maturation of nascent synapses. Here, we demonstrate that leucine-rich, glioma-inactivated protein 1 (LGI1), a secreted protein previously shown to modulate synaptic AMPA receptors, is a paracrine signal released from pre- and postsynaptic neurons that acts specifically through a disintegrin and metalloproteinase protein 22 (ADAM22) to set postsynaptic strength. We go on to describe a novel role for ADAM22 in maintaining excitatory synapses through PSD-95/Dlg1/zo-1 (PDZ) domain interactions. Finally, we show that in the absence of LGI1, the mature synapse scaffolding protein PSD-95, but not the immature synapse scaffolding protein SAP102, is unable to modulate synaptic transmission. These results indicate that LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of PSD-95.
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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.