Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and Characterization.

PMID 28426961


A gold standard for characterizing mechanically activated (MA) currents is via heterologous expression ofxa0candidate channels in naive cells. Two recent studies described MA channels using this paradigm. TMEM150c was proposed to be a component of an MA channel partly based on a heterologous expression approach (Hong etxa0al., 2016). In another study, Piezo1's N-terminal "propeller" domain was proposed to constitute an intrinsic mechanosensitive module based on expression of a chimera between a pore-forming domain of the mechanically insensitive ASIC1 channel and Piezo1 (Zhao etxa0al., 2016). When we attempted to replicate these results, we found each construct conferred modest MA currents in a small fraction of naive HEK cells similar to thexa0published work. Strikingly, these MA currents were not detected in cells in which endogenous Piezo1 was CRISPR/Cas9 inactivated. These results highlight the importance of choosing cells lacking endogenous MA channels to assay the mechanotransduction properties of various proteins. This Matters Arising paper is in response to Hong etxa0al. (2016) and Zhao etxa0al. (2016) in Neuron. See also the response papers by Hong etxa0al. (2017) and Zhao etxa0al. (2017) published concurrently with this Matters Arising.