The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels
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 vitr...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00006/full |
| _version_ | 1818233004476071936 |
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| author | Sara Baratchi Peter Keov Peter Keov Peter Keov William G. Darby Austin Lai Khashayar Khoshmanesh Peter Thurgood Parisa Vahidi Karin Ejendal Peter McIntyre |
| author_facet | Sara Baratchi Peter Keov Peter Keov Peter Keov William G. Darby Austin Lai Khashayar Khoshmanesh Peter Thurgood Parisa Vahidi Karin Ejendal Peter McIntyre |
| author_sort | Sara Baratchi |
| collection | DOAJ |
| description | 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 several members 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 20 min, as they translocate to the recycling endosomes and that the surface density is dependent on the release of calcium from the intracellular stores and is controlled via a PI3K, PKC, and RhoA signaling pathway. |
| first_indexed | 2024-12-12T11:15:17Z |
| format | Article |
| id | doaj.art-d32593cbbda246a08316fc463d02fa30 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T11:15:17Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d32593cbbda246a08316fc463d02fa302022-12-22T00:26:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-01-011010.3389/fphar.2019.00006432797The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 ChannelsSara Baratchi0Peter Keov1Peter Keov2Peter Keov3William G. Darby4Austin Lai5Khashayar Khoshmanesh6Peter Thurgood7Parisa Vahidi8Karin Ejendal9Peter McIntyre10School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaMolecular Pharmacology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, AustraliaSt Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaSchool of Engineering, RMIT University, Melbourne, VIC, AustraliaSchool of Engineering, RMIT University, Melbourne, VIC, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United StatesSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, AustraliaTRPV4 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 several members 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 20 min, as they translocate to the recycling endosomes and that the surface density is dependent on the release of calcium from the intracellular stores and is controlled via a PI3K, PKC, and RhoA signaling pathway.https://www.frontiersin.org/article/10.3389/fphar.2019.00006/fullTRPV4membrane traffickingendothelial cellsGSK1016790Acalcium |
| spellingShingle | Sara Baratchi Peter Keov Peter Keov Peter Keov William G. Darby Austin Lai Khashayar Khoshmanesh Peter Thurgood Parisa Vahidi Karin Ejendal Peter McIntyre The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels Frontiers in Pharmacology TRPV4 membrane trafficking endothelial cells GSK1016790A calcium |
| title | The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels |
| title_full | The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels |
| title_fullStr | The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels |
| title_full_unstemmed | The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels |
| title_short | The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels |
| title_sort | trpv4 agonist gsk1016790a regulates the membrane expression of trpv4 channels |
| topic | TRPV4 membrane trafficking endothelial cells GSK1016790A calcium |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00006/full |
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