ArticleMolecular genetics & genomic medicine2016
Identification of genetic variants of LGI1 and RTN4R (NgR1) linked to schizophrenia that are defective in NgR1-LGI1 signaling.
Article in Molecular genetics & genomic medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 11 citations in OpenAlex.
- A Tac1-Expressing Brainstem Pathway Underlies the Pathogenesis of Trigeminal Neuralgia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility.Translational psychiatry · 2017Article
- Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in Response to Strong Neuroexcitation.Frontiers in molecular neuroscience · 2017Article
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4 authors at 2 institutions in 1 country.
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Abstract
backgroundThe protein NgR1 is encoded by RTN4R, a gene linked to schizophrenia. We previously reported NgR1 as receptor for the epilepsy-linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation. Impairments in synapse formation are common in neurological disease and we hypothesized that an LGI1-NgR1 signaling pathway may contribute to the development of schizophrenia.
methodsWe screened two unrelated schizophrenic populations for variants in RTN4R and LGI1 using whole exome sequencing and Sanger sequencing. We tested the ability of LGI1 to bind rare coding variants of NgR1 using a cell surface binding assays and the signaling ability of NgR1 using COS7 cell-spreading assays.
resultsWe observed a previously reported rare coding variant in RTN4R (c.1195C>T, pR399W). We report the first LGI1 mutations to be identified in individuals with schizophrenia. Three different LGI1 mutations were found, two missense mutations (c.205G>A, p.V69I) and (c.313G>A, V105M), and an intronic variant (g.897T>C) that likely leads to a protein truncation. We found NgR1(R119W) and NgR1(277C) have a reduced ability to bind LGI1 in a cell surface binding assay. COS7 cell-spreading assays reveal that NgR1 mutants are impaired in their ability to mediate RhoA activation.
conclusionVariants in NgR1 and LGI1 may be associated with schizophrenia and variants in NgR1 found in schizophrenic patients have impaired LGI1-NgR1 signaling. Impaired LGI1-NgR1 signaling may contribute to disease progression.
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