{
  "abstract": "Cellular contractile forces regulate VE-cadherin dynamics, adhesion, and endothelial junction integrity. RhoA controls these forces through two parallel effector kinases: ROCK, which activates non-muscle myosin II motors, and SLK/LOK, which promote actin-membrane attachment through phosphorylation of ezrin, radixin, moesin proteins (ERM). How these two RhoA effector pathways differentially affect VE-cadherin dynamics at junctions is not known. Using single-molecule tracking of Halo-tagged VE-cadherin, we obtained a detailed characterization of VE-cadherin diffusive behavior inside and outside junctional regions in cultured human umbilical vein endothelial cells (HUVEC). VE-cadherin was substantially less mobile and more confined within junctions than in non-junctional membrane. Inhibiting ROCK with Y-27632 increased VE-cadherin mobility both inside and outside junctions, consistent with RhoA/ROCK-driven contractility restraining cadherin diffusion globally. Unexpectedly, inhibiting SLK/LOK produced the opposite effect, selectively reducing VE-cadherin mobility within junctions with no comparable change outside them. This effect was accompanied by an increase in reticular junctions, suggesting that SLK/LOK inhibition alters VE-cadherin mobility indirectly, through a change in junctional architecture, rather than through a direct effect of actin-membrane coupling on VE-cadherin itself. These findings identify SLK/LOK as a regulator of VE-cadherin dynamics acting in parallel to ROCK downstream of RhoA and point to junctional architecture as a previously unappreciated determinant of VE-cadherin mobility at endothelial cell-cell contacts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Tyler Nelson"
    },
    {
      "name": "Qiyao Lin"
    },
    {
      "name": "Zoya Quddoos"
    },
    {
      "name": "Henry Gatica-Gutierrez"
    },
    {
      "name": "Sofia Vargas-Hernandez"
    },
    {
      "name": "Arnold Hayer"
    },
    {
      "name": "Anna-Karin Gustavsson",
      "orcid": "0000-0002-0980-1168"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0ya40f2gs5kqj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762575",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762575v1.full",
  "id": "0ya40f2gs5kqj",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762575v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762575v1.full.pdf",
  "pmcid": "PMC13734074",
  "pmid": "42990554",
  "published": "2026-10-28",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/0ya40f2gs5kqj.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:22Z",
      "native_id": "10.64898/2026.10.28.762575",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762575v1"
    },
    {
      "first_seen": "2026-11-08T12:23:43Z",
      "native_id": "PMC13734074",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.28.762575"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "RhoA effectors ROCK and SLK/LOK oppositely regulate VE-cadherin mobility at endothelial junctions",
  "title_text": "RhoA effectors ROCK and SLK/LOK oppositely regulate VE-cadherin mobility at endothelial junctions",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:43Z",
  "url": "https://research.draconitic.com/paper/0ya40f2gs5kqj",
  "venue": "bioRxiv",
  "versions": []
}