TLNRD1 is a CCM complex component and regulates endothelial barrier integrity
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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 expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the four-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity and that the CCM2-TLNRD1 interaction impacts endothelial actin stress fiber and focal adhesion formation. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity.
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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 · see citing works
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 3,326 · see citing works
Cerebral cavernous malformations: from CCM genes to endothelial cell homeostasis
Fischer, A., Zalvide, J., Faurobert, E., Albiges-Rizo, C., & Tournier-Lasserve, E. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.02.004 · Cited by 199 · see citing works
Faurobert, E., Rome, C., Lisowska, J., Manet-Dupé, S., Boulday, G., Malbouyres, M., Balland, M., Bouin, A.-P., Kéramidas, M., Bouvard, D., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201303044 · Cited by 114 · see citing works
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- Authors
- Ball, N. J., Ghimire, S., Follain, G., Pajari, A. O., Wurzinger, D., 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
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2024-07-16
- Volume
- 223
- Issue
- 9
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC11252447
- OpenAlex
- W4400675925
- Cited by
- 11
- References
- 4
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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
- Biocenter Finland
- Research Council of Finland (338537, 325464, 332402)
- Sigrid Juselius Foundation
- Cancer Society of Finland
- Åbo Akademi University
- Academy of Finland (337530, 337531, 357910, 357911)
- Finnish Cancer Institute
- Centre of Excellence (# 346131)
- Jane and Aatos Erkko Foundation
- Biotechnology and Biological Sciences Research Council (BB/S007245/1)
- Cancer Research UK (CRUK-A21671)
- Topics
- Health Sciences › Medicine › 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
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