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Cortactin deficiency causes increased ROCK1‐mediated actin‐contractility and decreased adrenomedullin secretion leading to enhanced endothelial permeability (278.2)
Author(s) -
GarcíaPonce Alexander,
CitalánMadrid Alí,
VargasRobles Hilda,
Betanzos Abigail,
Rottner Klemens,
Vestweber Dietmar,
Schnoor Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.278.2
Subject(s) - cortactin , microbiology and biotechnology , chemistry , actin cytoskeleton , biology , cytoskeleton , biochemistry , cell
Changes in vascular permeability are a hallmark of inflammatory processes. The actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and thus permeability. We showed that the actin‐binding protein cortactin (CTTN) regulates vascular permeability in vivo via Rap1. However, it is not known if the actin cytoskeleton contributes to increased permeability after loss of CTTN. In a mass spectrometric analysis, we found Rho‐kinase1 (ROCK1) to be induced 2.7‐fold in cortactin‐KO endothelium. This was confirmed by Western blot and immunolabelling of tissues from CTTN‐KO mice. Concomitantly, we observed increased phosphorylation of MLC and more stress fibers in CTTN‐KO endothelium. Secretion of the hormone adrenomedullin (ADM), which activates Rap1 and counteracts formation of stress fibers, is reduced in CTTN‐KO serum and supernatant of CTTN‐depleted endothelium. Importantly, inhibition of ROCK1 or ADM administration rescued the effect on permeability provoked by loss of CTTN. Our data suggest that CTTN controls the molecular machinery necessary for the regulation of actomyosin contractility and vascular permeability. Grant Funding Source : Supported by CONACYT 179895