The TRPV4 agonist GSK1016790A regulates the membrane expression of TRPV4 channels

Baratchi, S, Keov, P, Darby, W, Lai, A, Khoshmanesh, K, Thurgood, P, Vahidi, P, Ejendal, K and McIntyre, P 2019, 'The TRPV4 agonist GSK1016790A regulates the membrane expression of TRPV4 channels', Frontiers in pharmacology, vol. 10, pp. 1-12.


Document type: Journal Article
Collection: Journal Articles

Title The TRPV4 agonist GSK1016790A regulates the membrane expression of TRPV4 channels
Author(s) Baratchi, S
Keov, P
Darby, W
Lai, A
Khoshmanesh, K
Thurgood, P
Vahidi, P
Ejendal, K
McIntyre, P
Year 2019
Journal name Frontiers in pharmacology
Volume number 10
Start page 1
End page 12
Total pages 12
Publisher Frontiers Research Foundation
Abstract TRPV4 is a non-selective cation channel that tunes the function of different tissues including the vascular endothelium, lung, chondrocytes, and neurons. GSK1016790A is the selective and potent agonist of TRPV4 and a pharmacological tool that is used to study the TRPV4 physiological function in vitro and in vivo. It remains unknown how the sensitivity of TRPV4 to this agonist is regulated. The spatial and temporal dynamics of receptors are the major determinants of cellular responses to stimuli. Membrane translocation has been shown to control the response of severalmembers of the transient receptor potential (TRP) family of ion channels to different stimuli. Here, we show that TRPV4 stimulation with GSK1016790A caused an increase in [Ca2+]i that is stable for a few minutes. Single molecule analysis of TRPV4 channels showed that the density of TRPV4 at the plasma membrane is controlled through two modes of membrane trafficking, complete, and partial vesicular fusion. Further, we show that the density of TRPV4 at the plasma membrane decreased within 20min, as they translocate to the recycling endosomes and that the surface density is dependent on the release of calciumfromthe intracellular stores and is controlled via a PI3K, PKC, and RhoA signaling pathway.
Subject Receptors and Membrane Biology
Keyword(s) TRPV4
membrane trafficking
endothelial cells
GSK1016790A
calcium
DOI - identifier 10.3389/fphar.2019.00006
Copyright notice © 2019 Baratchi, Keov, Darby, Lai, Khoshmanesh, Thurgood, Vahidi, Ejendal and McIntyre
ISSN 1663-9812
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