RT Journal Article
SR Electronic
T1 Voltage-gating of mechanosensitive PIEZO channels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156489
DO 10.1101/156489
A1 Mirko Moroni
A1 Martha Rocio Servin-Vences
A1 Raluca Fleischer
A1 Gary R. Lewin
YR 2017
UL http://biorxiv.org/content/early/2017/06/27/156489.abstract
AB Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage gated mode. Mutations that cause human diseases such as Xerocytosis profoundly shift voltage sensitivity of PIEZO1 channels towards the resting membrane potential and strongly promote pure voltage gating. Our data may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.