The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
TLNRD1 is a CCM complex component and regulates endothelial barrier integrity
Open accessPreprint — published as 10.1083/jcb.202310030 · Paper page
Abstract
We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is primarily expressed in the vasculature in vivo and that its depletion leads to vascular abnormalities in vivo and loss of barrier integrity in cultured endothelial cells. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct, high-affinity interaction with CCM2. Modeling and functional testing of TLNRD1 and CCM2 mutants reveal that their interaction is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the 4-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Notably, a CCM2 pathogenic mutation linked to vascular dementia in patients maps to the interface and disrupts the interaction. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity by controlling TLNRD1 bundling activity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 56
- 10.1038/nmeth.4074 · DOI
- 10.1111/j.1365-2818.2006.01706.x · DOI
- 10.1093/nar/gku936 · DOI · Paper page
- 10.1038/s41467-021-22518-0 · DOI
- 10.1001/jamaneurol.2018.3634 · DOI
- 10.1083/jcb.202005214 · DOI
- 10.1074/jbc.C900009200 · DOI
- 10.15252/emmm.201505433 · DOI
- 10.1083/jcb.201303044 · DOI · Paper page
- 10.1186/s13071-020-04428-0 · DOI
- 10.1016/j.molmed.2013.02.004 · DOI · Paper page
- 10.1074/jbc.M114.616433 · DOI
- 10.1016/j.febslet.2012.12.011 · DOI
- 10.1016/j.devcel.2018.02.015 · DOI
- 10.1074/jbc.M109.095455 · DOI
- 10.1101/578575 · DOI
- 10.1038/s41598-020-76603-3 · DOI
- 10.1016/j.yjmcc.2019.12.008 · DOI
- 10.1038/ng.321 · DOI
- 10.1093/hmg/ddn142 · DOI
- 10.1016/j.devcel.2017.08.015 · DOI
- 10.1016/j.cub.2018.11.053 · DOI
- 10.1172/jci.insight.126167 · DOI
- 10.1186/s40478-019-0789-0 · DOI
- 10.1093/nar/gkz365 · DOI
- 10.1101/2023.03.06.531398 · DOI
- 10.1038/s41580-022-00508-4 · DOI
- 10.1242/jcs.216093 · DOI
- 10.1016/j.ygeno.2014.12.002 · DOI
- 10.1038/s41586-020-2188-x · DOI · Paper page
- 10.2144/000112619 · DOI
- 10.1038/s41592-022-01488-1 · DOI · Paper page
- 10.1038/s41586-022-05165-3 · DOI
- 10.1038/s41431-020-00775-9 · DOI
- 10.1093/protein/2.2.93 · DOI
- Osmani, N. , G. Follain , V. Gensbittel , M.J. García-León , S. Harlepp , and J.G. Goetz . 2021. Probing Intravascular Adhesion and Extravasation of Tumor Cells with Microfluidics. In Metastasis: Methods and Protocols. U.S. Stein, editor. Springer US, New York, NY. 111–132. · DOI
- 10.1038/s41592-022-01663-4 · DOI · Paper page
- 10.1093/nar/gkab1038 · DOI · Paper page
- 10.1371/journal.pbio.3000202 · DOI
- 10.3390/cells10030704 · DOI
- 10.1038/s41586-018-0590-4 · DOI · Paper page
- 10.1038/nmeth.2019 · DOI · Paper page
- 10.1101/2022.11.01.514606 · DOI
- 10.1101/gr.1239303 · DOI · Paper page
- 10.3233/SAV-2010-0562 · DOI
- 10.1084/jem.20091258 · DOI
- 10.1098/rsob.200263 · DOI
- 10.1038/s41598-019-54845-0 · DOI
- Swamy, H. , and A.J. Glading . 2022. Is Location Everything? Regulation of the Endothelial CCM Signaling Complex. Front. Cardiovasc. Med. 9. · DOI
- 10.1093/nar/gky1131 · DOI · Paper page
- 10.1016/j.str.2015.04.003 · DOI
- 10.1038/nm.1911 · DOI
- 10.1038/s41556-023-01108-w · DOI
- 10.1172/jci.insight.160372 · DOI
- 10.1016/j.ydbio.2011.12.006 · DOI
- 10.1172/JCI39679 · DOI
Metadata
- Authors
- Ball, N. J., Ghimire, S., Follain, G., Pajari, A. O., Vaitkevičiūtė, M., Cowell, A. R., Berki, B., Ivaska, J., Paatero, I., Goult, B. T., & Jacquemet, G.
- Affiliations
- University of Liverpool (GB)
- Åbo Akademi University (FI)
- University of Kent (GB)
- Corresponding author
- Jacquemet, Guillaume
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- openRxiv
- Published
- 2023-09-29
- Volume
- 223
- Issue
- 9
- ISSN
- 0021-9525 (ISSN-L)
- PMC
- PMC11252447
- OpenAlex
- W4400675925
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion, other-oa)
- Åbo Akademi University Research Portal (submittedVersion, other-oa)
- Funders
- Helsingin Yliopisto
- Finnish Cancer Institute
- Cancer Research UK (A21671, BB/S007245/1, CRUK-A21671)
- Academy of Finland (325464, 337531, 332402, 357911, 337530, 338537, 357910, 346131)
- Jane ja Aatos Erkon Säätiö (337530)
- Turun Yliopisto
- Sigrid Juséliuksen Säätiö
- Syöpäjärjestöt
- Stiftelsen för Åbo Akademi
- Åbo Akademi
- Biocenter Finland (346131)
- Directorate for Biological Sciences
- Helsinki Institute of Life Science, Helsingin Yliopisto
- Biotechnology and Biological Sciences Research Council (BB/S007245/1)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Vascular Malformations Diagnosis and Treatment
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- CCM2, cerebral cavernous malformations, endothelial barrier integrity, actin bundling, actin cytoskeleton, focal adhesions, stress fibers, protein-protein interaction, subcellular localization, vascular integrity
- MeSH terms
- Actins, Animals, Carrier Proteins, Cell Nucleus, Humans, Actin Cytoskeleton, Protein Binding, Talin, Hemangioma, Cavernous, Central Nervous System, Focal Adhesions, Stress Fibers, Endothelial Cells, Mice, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
