ArticleProceedings of the National Academy of Sciences of the United States of America2017
Intersectin 1 is a component of the Reelin pathway to regulate neuronal migration and synaptic plasticity in the hippocampus.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 70 citations in OpenAlex.
- Epigenomic subtypes of late-onset Alzheimer's disease reveal distinct microglial signatures.Acta neuropathologica · 2026Article
- Intersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampus.Cellular and molecular life sciences : CMLS · 2025Article
- Should ITSN1 be considered as a Mendelian Parkinson's disease gene? Description of three novel families.NPJ Parkinson's disease · 2025Article
- Intersectin-1 enhances calcium-dependent replenishment of the readily releasable pool of synaptic vesicles during development.The Journal of physiology · 2025Article
- CircITSN1/EIF4A3/Itsn1 axis mediates postoperative cognitive dysfunction in aged mice: A novel mechanism and therapeutic target.Molecular therapy. Nucleic acids · 2025Article
- Genetic variants associated with age-related episodic memory decline implicate distinct memory pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.BMC genomics · 2024Article
- Article
- A clathrin mediated endocytosis scaffolding protein, Intersectin 1, changes in an isoform, brain region, and sex specific manner in Alzheimer's disease.Frontiers in neuroscience · 2024Article
- CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RNA alternative splicing.Nucleic acids research · 2022Article
- Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer's disease.Life science alliance · 2022Article
- Phenotype and genotype spectrum of variants in guanine nucleotide exchange factor genes in a broad cohort of Iranian patients.Molecular genetics & genomic medicine · 2022Article
- ITSN1: a novel candidate gene involved in autosomal dominant neurodevelopmental disorder spectrum.European journal of human genetics : EJHG · 2022Article
- Article
- Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders.Molecular neurobiology · 2021Article
- The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair.International journal of molecular sciences · 2021Review
- Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients.Scientific reports · 2021Article
- ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.Cellular and molecular life sciences : CMLS · 2021Article
- How Stress Influences the Dynamic Plasticity of the Brain's Extracellular Matrix.Frontiers in cellular neuroscience · 2021Review
- Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain development and function depend on the directed and coordinated migration of neurons from proliferative zones to their final position. The secreted glycoprotein Reelin is an important factor directing neuronal migration. Loss of Reelin function results in the severe developmental disorder lissencephaly and is associated with neurological diseases in humans. Reelin signals via the lipoprotein receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), but the exact mechanism by which these receptors control cellular function is poorly understood. We report that loss of the signaling scaffold intersectin 1 (ITSN1) in mice leads to defective neuronal migration and ablates Reelin stimulation of hippocampal long-term potentiation (LTP). Knockout (KO) mice lacking ITSN1 suffer from dispersion of pyramidal neurons and malformation of the radial glial scaffold, akin to the hippocampal lamination defects observed in VLDLR or ApoER2 mutants. ITSN1 genetically interacts with Reelin receptors, as evidenced by the prominent neuronal migration and radial glial defects in hippocampus and cortex seen in double-KO mice lacking ITSN1 and ApoER2. These defects were similar to, albeit less severe than, those observed in Reelin-deficient or VLDLR/ ApoER2 double-KO mice. Molecularly, ITSN1 associates with the VLDLR and its downstream signaling adaptor Dab1 to facilitate Reelin signaling. Collectively, these data identify ITSN1 as a component of Reelin signaling that acts predominantly by facilitating the VLDLR-Dab1 axis to direct neuronal migration in the cortex and hippocampus and to augment synaptic plasticity.
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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.