Second Messenger-Operated Calcium Entry Through TRPC6
Alexandre Bouron1,2, Sylvain Chauvet3,4, Stuart Dryer5,6
1Université Grenoble Alpes, 38000, Grenoble, France. alexandre.bouron@cea.fr.
Abstract:
Canonical transient receptor potential 6 (TRPC6) proteins assemble into heteromultimeric structures forming non-selective cation channels. In addition, many TRPC6-interacting proteins have been identified like some enzymes, channels, pumps, cytoskeleton-associated proteins, immunophilins, or cholesterol-binding proteins, indicating that TRPC6 are engaged into macromolecular complexes. Depending on the cell type and the experimental conditions used, TRPC6 activity has been reported to be controlled by diverse modalities. For instance, the second messenger diacylglycerol, store-depletion, the plant extract hyperforin or H2O2 have all been shown to trigger the opening of TRPC6 channels. A well-characterized consequence of TRPC6 activation is the elevation of the cytosolic concentration of Ca(2+). This latter response can reflect the entry of Ca(2+) through open TRPC6 channels but it can also be due to the Na(+)/Ca(2+) exchanger (operating in its reverse mode) or voltage-gated Ca(2+) channels (recruited in response to a TRPC6-mediated depolarization). Although TRPC6 controls a diverse array of biological functions in many tissues and cell types, its pathophysiological functions are far from being fully understood. This chapter covers some key features of TRPC6, with a special emphasis on their biological significance in kidney and blood cells.
Insights
Canonical transient receptor potential 6 (TRPC6) channels are key cation channels involved in various cellular functions. This review highlights TRPC6
Area of Science:
- Molecular Biology
- Cell Physiology
- Biochemistry
Background:
- Canonical transient receptor potential 6 (TRPC6) proteins form heteromultimeric non-selective cation channels.
- TRPC6 interacts with diverse proteins, forming macromolecular complexes involved in cellular signaling.
- TRPC6 activity is modulated by various factors, including diacylglycerol, store depletion, hyperforin, and H2O2.
Purpose of the Study:
- To review the key features of TRPC6 channels.
- To emphasize the biological significance of TRPC6 in kidney and blood cells.
- To discuss the diverse regulatory mechanisms and consequences of TRPC6 activation.
Main Methods:
- Literature review of TRPC6 channel function.
- Analysis of TRPC6 protein interactions and signaling pathways.
- Examination of TRPC6 roles in cellular calcium homeostasis.
Main Results:
- TRPC6 activation leads to elevated cytosolic Ca(2+) concentrations.
- Ca(2+) influx can occur via TRPC6 channels, reverse mode Na(+)/Ca(2+) exchanger, or voltage-gated Ca(2+) channels.
- TRPC6 plays a role in various biological functions across different tissues.
Conclusions:
- TRPC6 channels are crucial regulators of cellular ion transport and signaling.
- Understanding TRPC6 function is vital for elucidating its pathophysiological roles.
- Further research is needed to fully comprehend TRPC6's involvement in disease processes, particularly in renal and hematopoietic systems.
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