Rapid flow-induced activation of Gαq/11 is independent of Piezol activation

被引:18
作者
dela Paz, Nathaniel G. [1 ]
Frangos, John A. [1 ]
机构
[1] La Jolla Bioengn Inst, 505 Coast Blvd South,Suite 406, La Jolla, CA 92037 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2019年 / 316卷 / 05期
关键词
endothelial cells; G alpha(q/11); PECAM-1; PLA; shear stress; Piezo1; FLUID SHEAR-STRESS; ION-CHANNEL PIEZO1; ENDOTHELIAL-CELLS; GAMMA-SUBUNIT; VASCULAR DEVELOPMENT; BLOOD-PRESSURE; G-PROTEINS; ATP; MECHANISM; MEMBRANE;
D O I
10.1152/ajpcell.00215.2018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Endothelial cell (EC) mechanochemical transduction is the process by which mechanical stimuli are sensed by ECs and transduced into biochemical signals and ultimately into physiological responses. Identifying the mechanosensor/mechanochemical transducer(s) and describing the mechanism(s) by which they receive and transmit the signals has remained a central focus within the field. The heterotrimeric G protein, G alpha(q/11), is proposed to be part of a macromolecular complex together with PECAM-1 at EC junctions and may constitute the mechanochemical transducer as it is rapidly activated within seconds of flow onset. The mechanically activated cation channel Piezol has recently been implicated due to its involvement in mediating early responses. such as calcium and ATP release. Here, we investigate the role of Piezol in rapid shear stress-induced G alpha(q/11) activation. We show that flow-induced dissociation of G alpha(q/11) from PECAM-1 in ECs at 15 s is abrogated by BIM-46187, a selective inhibitor of G alpha(q/11) activation, suggesting that G alpha(q/11) activation is required for PECAM-1/G alpha(q/11) dissociation. Although siRNA knockdown of Piezol caused a dramatic decrease in PECAM-1/G alpha(q/11) association in the basal condition, it had no effect on flow-induced dissociation. Interestingly, siRNA knockdown of Piezol caused a marked decrease in PECAM-1 expression. Additionally, selective blockade of Piezol with ion channel inhibitors had no effect on flow-induced PECAM-1/G alpha(q/11) dissociations. Lastly. flow onset caused increased association of G beta(1) with Piezol as well as with the p101 subunit of phosphoinositide 3-kinase, which were both blocked by the GB gamma inhibitor gallein. Together, our results indicate that flow-induced activation of Piezol is not upstream of G protein activation.
引用
收藏
页码:C741 / C752
页数:12
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