Mechanisms of Proton Inhibition and Sensitization of the Cation Channel TRPV3

December 2020 in “ The Journal of General Physiology ”

Haiyuan Wang, Yang Pu, Yungang Lu, Jin Wang, Jaepyo Jeon, Qiaochu Wang, Jinbin Tian, Bin Zang, Ye Yu, Michael X. Zhu

TRPV3 cation channel hair morphogenesis skin barrier function extracellular acid intracellular protons aspartate residue glutamate residue epidermal barrier regulation

TLDR Acid can block TRPV3 from outside the cell but boost its function from inside.

The study explored how protons regulate the TRPV3 cation channel, which is crucial for hair morphogenesis and skin barrier function. Researchers found that extracellular protons inhibit TRPV3 activation through the aspartate residue D641, while intracellular protons sensitize the channel via C-terminal residues E682, E689, and D727. Mutations in these residues enhanced the channel's sensitivity to agonists and shifted it from a naive to a sensitized state. These findings provided insights into TRPV3's role in skin disorders and its regulation under acidic conditions, highlighting the complex interactions between protonation sites and channel function.