ArticleProceedings of the National Academy of Sciences of the United States of America2017
LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 124 citations in OpenAlex.
- Review
- CCR5-targeted allogeneic gamma-delta CD19 chimeric antigen receptor T cells for HIV-associated B cell-malignancy immunotherapy.Nature biomedical engineering · 2026Article
- Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.Cardiovascular research · 2026Article
- Biallelic LGI1 and ADAM23 variants cause hippocampal epileptic encephalopathy via the LGI1-ADAM22/23 pathway.Brain : a journal of neurology · 2025Article
- Structural insights into heterohexameric assembly of epilepsy-related ligand-receptor complex LGI1-ADAM22.eLife · 2025Article
- A hierarchy of PDZ domain scaffolding proteins clusters the Kv1 KScience advances · 2025Article
- 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
- Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.Molecular neurobiology · 2024Review
- LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic KNeurology(R) neuroimmunology & neuroinflammation · 2024Article
- OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Channelopathies in epilepsy: an overview of clinical presentations, pathogenic mechanisms, and therapeutic insights.Journal of neurology · 2024Review
- Activity-driven synaptic translocation of LGI1 controls excitatory neurotransmission.Cell reports · 2024Article
- Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity.Cell reports · 2024Article
- Rescue of Normal Excitability in LGI1-Deficient Epileptic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Movement disorders in autoimmune encephalitis: an update.Journal of neurology · 2023Review
- Adam, amigo, brain, and K channel.Biophysical reviews · 2023Review
- Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex.Neuroscience bulletin · 2023Article
- Comparative Effects of Domain-Specific Human Monoclonal Antibodies Against LGI1 on Neuronal Excitability.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis. Our data indicate that LGI1 is expressed at the axonal initial segment and regulates action potential firing by setting the density of the axonal Kv1.1 channels that underlie dendrotoxin-sensitive D-type potassium current. LGI1 deficiency incurs a >50% down-regulation of the expression of Kv1.1 and Kv1.2 via a posttranscriptional mechanism, resulting in a reduction in the capacity of axonal D-type current to limit glutamate release, thus contributing to epileptogenesis.
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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.