Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsGarcía Ponce, Alexander
Citalán Madrid, Alí F
Vargas Robles, Hilda
Chánez Paredes, Sandra
MetadataShow full item record
AbstractChanges in vascular permeability occur during inflammation and the actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and permeability. We demonstrated recently that the actin-binding protein cortactin regulates vascular permeability via Rap1. However, it is unknown if the actin cytoskeleton contributes to increased vascular permeability without cortactin. As we consistently observed more actin fibres in cortactin-depleted endothelial cells, we hypothesised that cortactin depletion results in increased stress fibre contractility and endothelial barrier destabilisation. Analysing the contractile machinery, we found increased ROCK1 protein levels in cortactin-depleted endothelium. Concomitantly, myosin light chain phosphorylation was increased while cofilin, mDia and ERM were unaffected. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in plasma from cortactin-deficient mice and in supernatants of cortactin-depleted endothelium. Importantly, adrenomedullin administration and ROCK1 inhibition reduced actomyosin contractility and rescued the effect on permeability provoked by cortactin deficiency in vitro and in vivo. Our data suggest a new role for cortactin in controlling actomyosin contractility with consequences for endothelial barrier integrity.
CitationLoss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility. 2016, 6:29003 Sci Rep
AffiliationDepartment for Molecular Biomedicine, Center of Research and Advanced Studies (CINVESTAV-IPN), 07360 Mexico-City, Mexico.
- Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis.
- Authors: Citalán-Madrid AF, Vargas-Robles H, García-Ponce A, Shibayama M, Betanzos A, Nava P, Salinas-Lara C, Rottner K, Mennigen R, Schnoor M
- Issue date: 2017 Sep
- Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.
- Authors: Schnoor M, Lai FP, Zarbock A, Kläver R, Polaschegg C, Schulte D, Weich HA, Oelkers JM, Rottner K, Vestweber D
- Issue date: 2011 Aug 1
- A novel approach to prevent endothelial hyperpermeability: the Crataegus extract WS® 1442 targets the cAMP/Rap1 pathway.
- Authors: Bubik MF, Willer EA, Bihari P, Jürgenliemk G, Ammer H, Krombach F, Zahler S, Vollmar AM, Fürst R
- Issue date: 2012 Jan
- The role of actin-binding proteins in the control of endothelial barrier integrity.
- Authors: García-Ponce A, Citalán-Madrid AF, Velázquez-Avila M, Vargas-Robles H, Schnoor M
- Issue date: 2015 Jan
- PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1/2-cortactin cross-talk.
- Authors: Stamatovic SM, Sladojevic N, Keep RF, Andjelkovic AV
- Issue date: 2015 Nov