The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
CCM1–ICAP-1 complex controls β1 integrin–dependent endothelial contractility and fibronectin remodeling
Open accessAbstract
The endothelial CCM complex regulates blood vessel stability and permeability. Loss-of-function mutations in CCM genes are responsible for human cerebral cavernous malformations (CCMs), which are characterized by clusters of hemorrhagic dilated capillaries composed of endothelium lacking mural cells and altered sub-endothelial extracellular matrix (ECM). Association of the CCM1/2 complex with ICAP-1, an inhibitor of β1 integrin, prompted us to investigate whether the CCM complex interferes with integrin signaling. We demonstrate that CCM1/2 loss resulted in ICAP-1 destabilization, which increased β1 integrin activation and led to increased RhoA-dependent contractility. The resulting abnormal distribution of forces led to aberrant ECM remodeling around lesions of CCM1- and CCM2-deficient mice. ICAP-1–deficient vessels displayed similar defects. We demonstrate that a positive feedback loop between the aberrant ECM and internal cellular tension led to decreased endothelial barrier function. Our data support that up-regulation of β1 integrin activation participates in the progression of CCM lesions by destabilizing intercellular junctions through increased cell contractility and aberrant ECM remodeling.
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“A recent report demonstrated that activation of β1-integrin due to loss of its inhibitor, ICAP-1, in human cerebral cavernous malformations, results in β1-integrin deposition in fibrillar adhesions, increased actin stress fibres and reduced endothelial barrier function35, suggesting that increased β1-integrin activity destabilizes intercellular junctions via increased cell contractility and”
From Endothelial destabilization by angiopoietin-2 via integrin β1 activation (2015) · cites this paper as [35]
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Metadata
- Authors
- Faurobert, E., Rome, C., Lisowska, J., Manet-Dupé, S., Boulday, G., Malbouyres, M., Balland, M., Bouin, A.-P., Kéramidas, M., Bouvard, D., Coll, J.-L., Ruggiero, F., Tournier-Lasserve, E., & Albiges-Rizo, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- INSERM U823, Institut Albert Bonniot, Grenoble F-38042, France 1
- École Normale Supérieure de Lyon (FR)
- INSERM, UMR-S 740, Université Paris Diderot, Paris F-75010, France 4
- Corresponding author
- Faurobert, Eva
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2013-08-05
- Volume
- 202
- Issue
- 3
- Pages
- 545-561
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3734079
- OpenAlex
- W2117038928
- Cited by
- 114
- References
- 83
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 15 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 15 · 2013: 3
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Clinical Neurology › Vascular Malformations Diagnosis and Treatment
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CCM1, CCM2, beta1 integrin, endothelial contractility, RhoA signaling, extracellular matrix remodeling, fibronectin, cerebral cavernous malformations, endothelial barrier function, intercellular junctions, vascular stability
- MeSH terms
- KRIT1 Protein, Animals, Cell Adhesion, Cells, Cultured, Fibronectins, Humans, Mice, Inbred Strains, Microtubule-Associated Proteins, Models, Biological, Proto-Oncogene Proteins, Mice, Knockout, Integrin beta1, Intracellular Signaling Peptides and Proteins, Mice, Human Umbilical Vein Endothelial Cells
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