Gating elements for carvacrol activation of the OTOP1 proton channel.

ABSTRACT: Otopetrin 1 (OTOP1) is a proton-activated channel crucial for animals' perception of sour taste. Despite its significance, the gating mechanism of OTOP1 remains poorly understood. Here, we demonstrate that carvacrol activates the mouse OTOP1 (mOTOP1) channel under neutral and acidic conditions. Functional analysis showed that carvacrol enhances pH fluorescence signals in OTOP1-expressing cells, with reduced efficacy at lower pH levels. Carvacrol selectively activates mOTOP1, while mOTOP2, mOTOP3, and Chelonia mydas OTOP1 (CmOTOP1) are insensitive to carvacrol activation under neutral pH. Through chimera and point mutation experiments, swapping S134 in transmembrane segment 3 (TM3) and T247 in the TM5-6 linker abolished carvacrol activation of mOTOP1 and conferred activation on CmOTOP1, sug

SUBMITTER: Hu J 

PROVIDER: S-EPMC11384762 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature