ArticleCells2020
Molecular Dissection of Neurodevelopmental Disorder-Causing Mutations in CYFIP2.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Expanding the Phenotype ofAnnals of the Child Neurology Society · 2025Article
- Impact of Genetic Variants Associated with Neurodevelopmental Disorders on the WAVE Regulatory Complex.Journal of chemical information and modeling · 2025Article
- Identification and validation of hub m7G-related genes and infiltrating immune cells in osteoarthritis based on integrated computational and bioinformatics analysis.BMC musculoskeletal disorders · 2025Article
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Molecular basis of the CYFIP2 and NCKAP1 autism-linked variants in the WAVE regulatory complex.Protein science : a publication of the Protein Society · 2025Article
- Common characteristics of variants linked to autism spectrum disorder in the WAVE regulatory complex.Frontiers in computational neuroscience · 2025Article
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- Article
- Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology.Brain : a journal of neurology · 2022Article
- Arf GTPase activates the WAVE regulatory complex through a distinct binding site.Science advances · 2022Article
- Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase.Nature communications · 2022Article
- Molecular Dynamics of CYFIP2 Protein and Its R87C Variant Related to Early Infantile Epileptic Encephalopathy.International journal of molecular sciences · 2022Article
- Experimental verification and comprehensive analysis of m7G methylation regulators in the subcluster classification of ischemic stroke.Frontiers in genetics · 2022Article
- Cytoplasmic FMR1 interacting protein (CYFIP) family members and their function in neural development and disorders.Molecular biology reports · 2021Review
- Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- WASP family proteins: Molecular mechanisms and implications in human disease.European journal of cell biologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actin remodeling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies described de novo mutations in the CYFIP2 subunit of WRC, which caused intellectual disability (ID) in humans. Although mutations had been proposed to effect WRC activation, no experimental evidence for this was provided. Here, we made use of CRISPR/Cas9-engineered B16-F1 cell lines that were reconstituted with ID-causing CYFIP variants in different experimental contexts. Almost all CYFIP2-derived mutations (7 out of 8) promoted WRC activation, but to variable extent and with at least two independent mechanisms. The majority of mutations occurs in a conserved WAVE-binding region, required for WRC transinhibition. One mutation is positioned closely adjacent to the Rac-binding A site and appears to ease Rac-mediated WRC activation. As opposed to these gain-of-function mutations, a truncating mutant represented a loss-of-function variant and failed to interact with WRC components. Collectively, our data show that explored CYFIP2 mutations frequently, but not always, coincide with WRC activation and suggest that normal brain development requires a delicate and precisely tuned balance of neuronal WRC activity.
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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.