Fig. 1. Deletion of IDR2, IDR3 and IDR5 alters membrane indentation-evoked PIEZO2 currents.

a Top and side view of the mouse PIEZO2 structure. IDR regions were modeled with SWISS-MODEL and combined with the partial cryo-EM PIEZO2 structure (6KG7). Note, QMEAN-values of the IDRs were low and thus the model solely serves as an orientation guide for the approximate size and localization of the IDRs. b mPIEZO2 amino acid sequence-based disorder predictions (bottom) determined using IUPRED-L (blue), PONDR-VSL2b (black) and ESpritz-N (gray). Positions of the IDRs are indicated above the graph. c Recording configuration cartoon and example traces of whole-cell currents evoked by mechanical indentation of N2a cells expressing PIEZO2 (black, left), IDR3^del (purple, middle) and IDR5^del (blue, right). d Displacement-responses curves of peak current amplitudes of PIEZO2, IDR^del mutants and empty vector in N2a-P1KO cells. Symbols are mean ± s.e.m. N-numbers vary within groups because large mechanical stimuli occasionally damage the cells; PIEZO2 (N_{0.4–4 µm} = 35, N_4.4 µm = 33, N_4.8 µm = 30, N_5.2 µm = 29), IDR1^del (N = 10), IDR2^del (N_{0.4–4 µm} = 9, N_4.4 µm = 8, N_4.8 µm = 6, N_5.2 µm = 5), IDR3^del (N_{0.4–4.4 µm} = 16, N_4.8 µm = 14, N_5.2 µm = 13), IDR4^del (N_{0.4–4.4 µm} = 19, N_4.8 µm = 17, N_5.2 µm = 16), IDR5^del (N = 22), IDR6^del (N_{0.4–4.8 µm} = 9, N_5.2 µm = 6), IDR7^del (N_{0.4–2.8 µm} = 18, N_3.2 µm = 16, N_{3.6–4.0 µm} = 15 N_4.4 µm = 13, N_4.8 µm = 11, N_5.2 µm = 7), empty vector (N = 15). Comparison with Kruskal–Wallis test and Dunn’s post-test. P-values for PIEZO2 vs IDR5^del (from left to right): ***0.0000007, ***0.0000003, ***0.0000002, ***0.000001, ***0.000002, ***0.00002, ***0.000138, ***0.000041. P-values for PIEZO2 vs IDR3^del (from left to right): ^#0.0239, ^#0.0232, ^##0.0054, ^#0.0186, ^##0.0098. e Comparison of the inactivation time constants (τ_inact) of PIEZO2 and IDR^del-mutants using with Kruskal–Wallis (p = 0.1531). N-numbers are indicated within bars. f Example traces of PIEZO2 and IDR2^del currents evoked by stimuli of different velocities and (g) comparison of the current amplitude ratios (I_0.25µm/ms/I_1µm/ms) of PIEZO2 and all IDR-deletions using One-Way ANOVA, F(7, 114) = 3.771 and Dunnett’s post-test (PIEZO2 vs IDR2^del, ***p = 0.0002). Bars represent means ± s.e.m with ratios values from individual cells shown as black circles and N-numbers per group being indicated above the bars. Source data are provided as a Source Data file.