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Transient Receptor Potential Canonical (TRPC) Channels: Then and Now
Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster T...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565274/ https://www.ncbi.nlm.nih.gov/pubmed/32872338 http://dx.doi.org/10.3390/cells9091983 |
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author | Chen, Xingjuan Sooch, Gagandeep Demaree, Isaac S. White, Fletcher A. Obukhov, Alexander G. |
author_facet | Chen, Xingjuan Sooch, Gagandeep Demaree, Isaac S. White, Fletcher A. Obukhov, Alexander G. |
author_sort | Chen, Xingjuan |
collection | PubMed |
description | Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca(2+) and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca(2+) concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools. |
format | Online Article Text |
id | pubmed-7565274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75652742020-10-26 Transient Receptor Potential Canonical (TRPC) Channels: Then and Now Chen, Xingjuan Sooch, Gagandeep Demaree, Isaac S. White, Fletcher A. Obukhov, Alexander G. Cells Review Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca(2+) and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca(2+) concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools. MDPI 2020-08-28 /pmc/articles/PMC7565274/ /pubmed/32872338 http://dx.doi.org/10.3390/cells9091983 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Chen, Xingjuan Sooch, Gagandeep Demaree, Isaac S. White, Fletcher A. Obukhov, Alexander G. Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title | Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title_full | Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title_fullStr | Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title_full_unstemmed | Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title_short | Transient Receptor Potential Canonical (TRPC) Channels: Then and Now |
title_sort | transient receptor potential canonical (trpc) channels: then and now |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565274/ https://www.ncbi.nlm.nih.gov/pubmed/32872338 http://dx.doi.org/10.3390/cells9091983 |
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