Rapid flow-induced activation of Gαq/11 is independent of Piezo1 activation

American Journal of Physiology. Cell Physiology
Nathaniel G dela Paz, John A Frangos

Abstract

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, Gαq/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 Piezo1 has recently been implicated due to its involvement in mediating early responses, such as calcium and ATP release. Here, we investigate the role of Piezo1 in rapid shear stress-induced Gαq/11 activation. We show that flow-induced dissociation of Gαq/11 from PECAM-1 in ECs at 15 s is abrogated by BIM-46187, a selective inhibitor of Gαq/11 activation, suggesting that Gαq/11 activation is required for PECAM-1/Gαq/11 dissociation. Although siRNA knockdown of Piezo1 caused a dramatic decrease in PECAM-1/Gαq/11 association in the basal condition, it had no effect on flow-induced d...Continue Reading

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Citations

Sep 20, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·David J Beech, Antreas C Kalli
Apr 1, 2020·EMBO Reports·John Smith Del RosarioTibor Rohacs
May 20, 2020·Chemistry : a European Journal·Michael GütschowEvi Kostenis
Dec 21, 2019·Nature Communications·Serap ErdogmusMichael Mederos Y Schnitzler
Aug 28, 2020·Frontiers in Physiology·Etienne RouxThierry Couffinhal
Feb 6, 2021·Cytoskeleton·Keiichiro TanakaMartin A Schwartz

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Methods Mentioned

BETA
transfection
proximity ligation assay
confocal microscopy
proximity
fluorescence resonance
FRET
BRET

Software Mentioned

Zeiss LSM Image Browser
ImageJ

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