Fig. 4

Mutations causing xerocytosis in humans alter voltage modulation of PIEZO1. a Current responses to a pressure stimulation of 70 mmHg during 300 ms voltage steps ranging from 0 to 150 mV, followed by a repolarization step to −60 mV to obtain tail currents for wild-type PIEZO1 (black), R2482H (blue), R2482K (red), R1353T (green), A2036T (orange), T2143 (magenta), and R2482A (gray) mutants. The R2482K mutant shows decreased voltage modulation. b Tail currents from individual cells were normalized to their maximum and fitted to a Boltzmann relationship (wt: V₅₀ = 91.9 ± 3.2 mV, slope 22.2 ± 0.9, 12 cells; R2482H V₅₀ = 42.0 ± 3.7 mV, slope 14.4 ± 1.5, 19 cells; R2482K V₅₀ 27.2 ± 5.9 mV, slope 12.2 ± 1.5, 10 cells, R1353P V₅₀ = 82.4 ± 8.8 mV, slope 20.1 ± 1.3, 8 cells, A2036T V₅₀ = 82.4 ± 10.2 mV, slope 22.4 ± 0.9, 5 cells; T2143M V₅₀ = 28.7 ± 8.8 mV, slope 17.6 ± 2.0, 8 cells; R2482A V₅₀ = 45.5 ± 5.4 mV, slope 15.1 ± 2.1, 10 cells. One-way ANOVA, Dunnett’s post-test, significance P < 0.0001, dF = 72). Pooled data are shown as mean ± SEM. c 3D structure of the trimeric mPIEZO1 showing the position of the mutants involved in xerocytosis²¹. R1353 is located on the beam and is not shown. R2482 is in the bottom of the inner helix, A2036 is located in a peripheral helix, and T2143 is in the anchor domain. Molecular graphic was performed with the UCSF Chimera package