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Role of the focal adhesion protein Zyxin in wall tension‐induced endothelial signaling
Author(s) -
Babu Sahana Suresh,
Kuhn Michaela,
Hecker Markus,
Cattaruzza Marco
Publication year - 2011
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.25.1_supplement.39.11
Subject(s) - focal adhesion , microbiology and biotechnology , adhesion , tension (geology) , signal transduction , chemistry , biology , materials science , organic chemistry , ultimate tensile strength , metallurgy
Wall tension‐induced endothelial signaling is poorly understood. We here define a wall tension‐induced signaling cascade specifically leading to activation of the focal adhesion protein zyxin which then, as a mechanotransducer and transcription factor, orchestrates endothelial gene expression. Using human primary cultured endothelial cells subjected to cyclic stretch (10% elongation at 0.5 Hz for 10 min. to 6 h) we show that wall tension leads to the TRP‐C channel‐induced release of endothelin‐1. This then leads to an ETB receptor‐mediated atrial natriuretic peptide (ANP) release and, finally, to ANP‐induced ANP receptor A (NPR‐A)/cGMP‐mediated activation of the protein kinase cGKI. Similar data were obtained using pressure‐perfused arterial segments from wild type mice and mice deficient in TRP‐C channel(s) or NPR‐A. Activation of this pathway results in the phosphorylation of zyxin at serine‐142 which is sufficient to drive its translocation to the nucleus where it induces complex changes in mechanosensitive gene expression. These findings describe for the first time a wall tension‐induced signaling cascade leading to changes in the endothelial cell phenotype that is reminiscent to endothelial dysfunction at the onset of pressure‐induced vascular remodeling.