Understanding the molecular components of mechanically evoked currents in the Merkel cell line MCC13

Merkel cells are epithelial cells involved in the discrimination of light touch. Situated in the skin, these specialized cells decode mechanical cues through the mechanosensitive ion channel PIEZO2. Merkel cell carcinoma lines have been widely used as in vitro models for Merkel cells and like the native cell, they exhibit mechanically evoked currents. Herein, we show that unlike the native Merkel cell, which principally uses PIEZO2, mechanically evoked currents in the Merkel cell carcinoma line MCC13 are predominantly carried by PIEZO1, with variable contributions from PIEZO2. Slowly inactivating current types in these cells are carried by PIEZO1 in complex with auxiliary subunits MDFIC or MDFI. Moreover, PIEZO1 strongly influences the endogenous levels of MDFIC, a known transcriptional repressor, whereby the loss of PIEZO1 dramatically reduced cellular levels of MDFIC. This suggests that the removal of PIEZO1 from a cell will likely have influences on the cellular transcriptome beyond its canonical Ca2+-based signalling pathways. In conclusion, utilizing MCC13 cells as a simple in vitro model of native Merkel cell mechanotransduction should be carried out with caution.