Molecular Studies of Transient Receptor Potential Vanilloid 3 (TRPV3)

This thesis explores the role of the TRPV3 ion channel, primarily expressed in skin keratinocytes, in various physiological processes and its involvement in skin diseases. The study successfully generated a stable human TRPV3 cell line and investigated the channel's function in lung cancer cells (A549) and keratinocytes. It was found that GPCRs do not sensitize or open TRPV3 channels but instead desensitize them to the agonist 2-APB. Novel agonists for TRPV3 were identified, and the study revealed that repeated stimulation potentiates TRPV3 activity, potentially due to phosphorylation. A significant finding was the novel role of TRPV3 in mechanotransduction, where shear stress sensitizes the channel, enhancing its response to 2-APB. This research contributes to understanding TRPV3's physiological activation and regulation, particularly in the endothelium and skin.