Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

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Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

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作者：Sara Baratchi ; Juhura G. Almazi ; William Darby…
关键词：TRPV4 ; Endothelium ; Shear stress ; Translocation ; Ca2+ ; Mechanotransduction
刊名：Cellular and Molecular Life Sciences (CMLS)
出版年：2016
出版时间：February 2016
年：2016
卷：73
期：3
页码：649-666
全文大小：4,166 KB
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作者单位：Sara Baratchi (1)
Juhura G. Almazi (1)
William Darby (1)
Francisco J. Tovar-Lopez (2)
Arnan Mitchell (2)
Peter McIntyre (1)

1. School of Medical Sciences and Health Innovations Research Institute, RMIT University, Melbourne, VIC, 3083, Australia
2. School of Electrical and Computer Engineering, RMIT University, Melbourne, VIC, 3001, Australia
刊物类别：Biomedical and Life Sciences
刊物主题：Life Sciences
Cell Biology
Biomedicine
Life Sciences
Biochemistry
出版者：Birkh盲user Basel
ISSN：1420-9071

文摘

Mechanosensitive ion channels are implicated in the biology of touch, pain, hearing and vascular reactivity; however, the identity of these ion channels and the molecular basis of their activation is poorly understood. We previously found that transient receptor potential vanilloid 4 (TRPV4) is a receptor operated ion channel that is sensitised and activated by mechanical stress. Here, we investigated the effects of mechanical stimulation on TRPV4 localisation and activation in native and recombinant TRPV4-expressing cells. We used a combination of total internal reflection fluorescence microscopy, cell surface biotinylation assay and Ca2+ imaging with laser scanning confocal microscope to show that TRPV4 is expressed in primary vascular endothelial cells and that shear stress sensitises the response of TRPV4 to its agonist, GSK1016790A. The sensitisation was attributed to the recruitment of intracellular pools of TRPV4 to the plasma membrane, through the clathrin and dynamin-mediated exocytosis. The translocation was dependent on ILK/Akt signalling pathway, release of Ca2+ from intracellular stores and we demonstrated that shear stress stimulated phosphorylation of TRPV4 at tyrosine Y110. Our findings implicate calcium-sensitive TRPV4 translocation in the regulation of endothelial responses to mechanical stimulation. Keywords TRPV4 Endothelium Shear stress Translocation Ca2+ Mechanotransduction