ArticleNature communications2017
An autism spectrum disorder-related de novo mutation hotspot discovered in the GEF1 domain of Trio.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 120 citations in OpenAlex.
- Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia.Biology · 2026Review
- Trio and CRMP2 regulate axon branching and Semaphorin3A signaling.Communications biology · 2025Article
- Advancing precision diagnosis in autism: Insights from large-scale genomic studies.Molecules and cells · 2025Review
- Oligodendrocyte myelin glycoprotein impairs dendritic arbors via schizophrenia risk gene Trio.Neurobiology of disease · 2025Article
- Article
- Unraveling the impact of genetic variants.eLife · 2025Article
- The Rho GEF Trio functions in contact inhibition of locomotion of neural crest cells by interacting with Ptk7.Development (Cambridge, England) · 2025Article
- Both GEF domains of the autism and developmental epileptic encephalopathy-associated Trio protein are required for proper tangential migration of GABAergic interneurons.Molecular psychiatry · 2025Article
- Common Genetic Variants inGenetics research · 2025Article
- Biochemical Properties of Synaptic Proteins Are Dependent on Tissue Preparation: NMDA Receptor Solubility Is Regulated by the C-Terminal Tail.Journal of cellular biochemistry · 2025Article
- Dentate Gyrus Morphogenesis is Regulated by an Autism Risk Gene Trio Function in Granule Cells.Neuroscience bulletin · 2025Article
- Genetic Diversity in Schizophrenia: Developmental Implications of Ultra-Rare, Protein-Truncating Mutations.Genes · 2024Review
- Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?Lipids in health and disease · 2024Article
- Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach.Molecular autism · 2024Article
- Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes.Nature reviews. Neurology · 2024Review
- TRIOBP modulates β-catenin signaling by regulation of miR-29b in idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2023Article
- Protein 4.1N Plays a Cell Type-Specific Role in Hippocampal Glutamatergic Synapse Regulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- Interneuron odyssey: molecular mechanisms of tangential migration.Frontiers in neural circuits · 2023Review
- Comparing synaptic proteomes across five mouse models for autism reveals converging molecular similarities including deficits in oxidative phosphorylation and Rho GTPase signaling.Frontiers in aging neuroscience · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Rho guanine nucleotide exchange factor (RhoGEF) Trio promotes actin polymerization by directly activating the small GTPase Rac1. Recent studies suggest that autism spectrum disorder (ASD)-related behavioral phenotypes in animal models of ASD can be produced by dysregulation of Rac1's control of actin polymerization at glutamatergic synapses. Here, in humans, we discover a large cluster of ASD-related de novo mutations in Trio's Rac1 activating domain, GEF1. Our study reveals that these mutations produce either hypofunctional or hyperfunctional forms of Trio in rodent neurons in vitro. In accordance with pathological increases or decreases in glutamatergic neurotransmission observed in animal models of ASD, we find that these mutations result in either reduced synaptic AMPA receptor expression or enhanced glutamatergic synaptogenesis. Together, our findings implicate both excessive and reduced Trio activity and the resulting synaptic dysfunction in ASD-related pathogenesis, and point to the Trio-Rac1 pathway at glutamatergic synapses as a possible key point of convergence of many ASD-related genes.Trio is a RhoGEF protein that promotes actin polymerization and is implicated in the regulation of glutamatergic synapses in autism spectrum disorder (ASD). Here the authors identify a large cluster of de novo mutations in the GEF1 domain of Trio in whole-exome sequencing data from individuals with ASD, and confirm that some of these mutations lead to glutamatergic dysregulation in vitro.
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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.