{
  "abstract": "The Arg87Cys mutation in CYFIP2 has been implicated in early-onset developmental and epileptic encephalopathy (DEE), yet its molecular consequences remain incompletely understood. CYFIP2 functions as part of the WAVE regulatory complex (WRC), where it plays a key role in actin filament polymerization and interacts with RNA-binding proteins (RBPs) to regulate mRNA translation. Previous studies have demonstrated that this mutation alters the structure of CYFIP2, resulting in a gain of function in the WRC. Additionally, the mutation appears to promote the formation of intracellular granules that colocalize with RBPs; however, the impacts of this mutation on these interactions remain unclear. Here, we combined cross-linking mass spectrometry (XL-MS) and label-free quantitative proteomics to investigate how this mutation alters the protein interactome and actin regulatory pathways. XL-MS data revealed exclusive cross-links between actin and tropomyosin isoforms in the Arg87Cys variant, suggesting altered cytoskeletal dynamics. Quantitative proteomic analysis of patient-derived neural progenitor cells corroborated these findings by revealing an increase in the abundance of stress-fiber-associated proteins. Altogether, our results point to a broader impact of CYFIP2 mutations on cytoskeletal organization and protein interaction networks with potential implications beyond the nervous system. This is the first study to our knowledge to suggest a link between the Arg87Cys mutation and dysregulation of stress-fiber-related proteins, indicating possible disruption of other actin-processing pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Fundação Oswaldo Cruz (Fiocruz) , , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ísis V. Biembengut"
    },
    {
      "affs": [
        0
      ],
      "name": "Emanuella de C. Andreassa"
    },
    {
      "affs": [
        0
      ],
      "name": "Marlon D. M. dos Santos",
      "orcid": "0000-0002-1178-1266"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle L. Z. Silva"
    },
    {
      "affs": [
        0
      ],
      "name": "Louise U. Kurt",
      "orcid": "0000-0002-9703-7226"
    },
    {
      "affs": [
        0
      ],
      "name": "Patrícia Shigunov"
    },
    {
      "affs": [
        0
      ],
      "name": "Paulo C. Carvalho"
    },
    {
      "affs": [
        0
      ],
      "name": "Tatiana A. C. B. de Souza",
      "orcid": "0000-0002-1850-6080"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9fp54ps5tgsnj.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.5c12192",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718196/?tool=EBI",
  "id": "9fp54ps5tgsnj",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/11/42/64371/5448925/The-CYFIP2-Arg87Cys-Mutation-Reshapes-the",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
    ]
  ],
  "openalex": "W7221542422",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.5c12192",
  "pmcid": "PMC13718196",
  "pmid": "42959718",
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/9fp54ps5tgsnj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.5c12192",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/11/42/64371/5448925/The-CYFIP2-Arg87Cys-Mutation-Reshapes-the"
    },
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13718196",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13718196"
    },
    {
      "first_seen": "2026-11-01T00:20:52Z",
      "native_id": "MED:42959718",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959718"
    },
    {
      "first_seen": "2026-11-02T12:22:17Z",
      "native_id": "PMC13718196",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acsomega.5c12192"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "The CYFIP2 Arg87Cys Mutation Reshapes the Interactome and Alters Stress Fiber-Associated Proteins",
  "title_text": "The CYFIP2 Arg87Cys Mutation Reshapes the Interactome and Alters Stress Fiber-Associated Proteins",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:17Z",
  "url": "https://research.draconitic.com/paper/9fp54ps5tgsnj",
  "venue": "ACS Omega",
  "versions": []
}