title: Rapid changes in shear stress induce dissociation of a G alpha(q/11)-platelet endothelial cell adhesion molecule-1 complex.
abstract: 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 G alpha(q/11) also mediate flow-induced responses. Here, we investigated whether PECAM-1 and G alpha(q/11) could act in unison to rapidly respond to fluid shear stress. With immunohistochemistry, we observed a co-localization of G alpha(q/11) and PECAM-1 at the cell-cell junction in the atheroprotected section of mouse aortae. In contrast, G alpha(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 G alpha(q/11)-PECAM-1 complex within 30 s and a partial relocalization of the G alpha(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 G alpha(q/11)-PECAM-1 dissociation. These results allow us to conclude that G alpha(q/11)-PECAM-1 forms a mechanosensitive complex and its localization suggests the G alpha(q/11)-PECAM-1 complex is a critical mediator of vascular diseases.
authors.affiliation: La Jolla Bioengineering Institute, 505 Coast Blvd South, La Jolla, CA 92037, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Otte
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Bell
authors.forename: Laurent
authors.initials: L
authors.lastname: Loufrani
authors.forename: Jiunn-Chern
authors.initials: JC
authors.lastname: Yeh
authors.forename: Benoît
authors.initials: B
authors.lastname: Melchior
authors.forename: Diep N
authors.initials: DN
authors.lastname: Dao
authors.forename: Hazel Y
authors.initials: HY
authors.lastname: Stevens
authors.forename: Charles R
authors.initials: CR
authors.lastname: White
authors.forename: John A
authors.initials: JA
authors.lastname: Frangos