TMC4 localizes to multiple taste cell types in the mouse taste papillae.

Salty taste is mediated through two distinct transduction pathways: the amiloride-sensitive and amiloride-insensitive (AI). Transmembrane channel-like 4 (TMC4), a voltage-dependent chloride channel, has recently been identified as playing a critical role in AI-mediated salt taste responses. Although its functional properties have been demonstrated, the specific taste cell types that express TMC4 have not been fully characterized. To investigate the cellular localization of TMC4, we generated Tmc4-EGFP knock-in mice and performed immunohistochemical analyses of the taste papillae. By performing multiple fluorescent immunostaining with cell-type-specific markers, such as KCNQ1 (type I-III), Gustducin and PLCβ2 (type II), and AADC (type III), together with EGFP, we found that over 98% of EGFP-positive cells overlapped with the signal of all three taste cell type markers in the circumvallate papillae of Tmc4-EGFP mice. In the fungiform papillae, 95.9% of EGFP-positive cells colocalized with KCNQ1. These results demonstrate that TMC4 is broadly expressed across all three taste cell types, and suggest the possible involvement of multiple, functionally distinct taste cell populations in AI-mediated salty taste transduction.