S100A4 plays a key role in TRPV3 ion channel expression and its electrophysiological function.

Transient receptor potential vanilloid 3 (TRPV3), a non-selective cation ion channel, is regulated by small molecules such as Ca2+ and calmodulin (CaM). Together with S100A4 (S100 calcium-binding protein family), is critical in cell proliferation and progression. Although TRPV3 has been proved to play a role in Ca2+ regulation and participate in Ca2+-related cellular processes, its molecular mechanism remains unclear. In this study, we found that TRPV3 and S100A4 were co-expressed in the same region of the cell, and surprisingly, the protein expression level of TRPV3 significantly increased with the overexpression of S100A4. Moreover, co-immunoprecipitation results showed that these two proteins could bind with each other. Functionally, we found that when S100A4 was simultaneously expressed in cells, more Ca2+ would be transferred into the cells through the TRPV3 ion channel. Consistent with Ca2+ regulation results, electrophysiological recordings demonstrated that S100A4 improved the function of TRPV3 in ions' flux, suggesting that the S100A4 could bind with TRPV3 and simultaneously promoted its expression, thus affecting its functions on related ions' flux. Our findings identified the link between S100A4 and TRPV3 and provided a novel molecular mechanism for TRPV3 regulation.