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Rapid changes in shear stress induce dissociation of a Gα q/11 –platelet endothelial cell adhesion molecule‐1 complex
Author(s) -
Otte Laura A.,
Bell Kelly S.,
Loufrani Laurent,
Yeh JiunnChern,
Melchior Benoît,
Dao Diep N.,
Stevens Hazel Y.,
White Charles R.,
Frangos John A.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.172643
Subject(s) - mechanosensitive channels , microbiology and biotechnology , endothelial stem cell , shear stress , gq alpha subunit , chemistry , cell adhesion molecule , endothelium , biophysics , biology , signal transduction , g protein , biochemistry , receptor , ion channel , endocrinology , in vitro , materials science , composite material
It has been recently shown that endothelial platelet endothelial cell adhesion molecule‐1 (PECAM‐1) expression is pro‐atherogenic. PECAM‐1 is involved in sensing rapid changes in fluid shear stress but the mechanisms for activating signalling complexes at the endothelial cell junction have yet to be elucidated. Additional studies suggest the activation of membrane‐bound G proteins Gα q/11 also mediate flow‐induced responses. Here, we investigated whether PECAM‐1 and Gα q/11 could act in unison to rapidly respond to fluid shear stress. With immunohistochemistry, we observed a co‐localization of Gα q/11 and PECAM‐1 at the cell–cell junction in the atheroprotected section of mouse aortae. In contrast, Gα q/11 was absent from junctions in atheroprone areas as well as in all arterial sections of PECAM‐1 knockout mice. In primary human endothelial cells, temporal gradients in shear stress led to a rapid dissociation of the Gα q/11 –PECAM‐1 complex within 30 s and a partial relocalization of the Gα q/11 staining to perinuclear areas within 150 min, whereas transitioning fluid flow devoid of temporal gradients did not disrupt the complex. Inhibition of G protein activation eliminated temporal gradient flow‐induced Gα q/11 –PECAM‐1 dissociation. These results allow us to conclude that Gα q/11 –PECAM‐1 forms a mechanosensitive complex and its localization suggests the Gα q/11 –PECAM‐1 complex is a critical mediator of vascular diseases.