Fig. 1.

Pathogenic GBA1 disrupts ER Ca²⁺ release. (A–D) ER Ca²⁺ release in GBA1^wt/wt₅₅, GBA1^mut/mut₅₅^GD and GBA1^wt/mut₅₅^PD cells (young cohort). (A) Cytosolic Ca²⁺ recordings from individual fibroblasts challenged with thapsigargin (1 μM) from the indicated representative populations. Experiments were performed in the absence of extracellular Ca²⁺. (B) Summary data (mean ± SEM) quantifying the magnitude of thapsigargin-evoked Ca²⁺ signals in the indicated number of fields of view. Results are from 5 to 9 independent passages analysing 154–367 cells. (C) Cytosolic Ca²⁺ recordings from individual fibroblasts stimulated with cADPR-AM (25 μM). Experiments were performed in the presence of extracellular Ca²⁺. (D) Summary data quantifying the percentage of cells responsive to cADPR. Results are from 2 to 3 independent passages analysing 39–75 cells. (E) Similar to A except thapsigargin-evoked Ca²⁺ release was assessed in GBA1^wt/wt₅₅, GBA1^wt/mut₅₈^ASX and GBA1^wt/mut₅₅^PD cells. (F) Summary data from 4 independent passages analysing 46–127 cells. (G) Similar to C except cADPR-evoked Ca²⁺ release was assessed in GBA1^wt/wt₅₅, GBA1^wt/mut₅₈^ASX and GBA1^wt/mut₅₅^PD cells. (H) Summary data from 3 to 6 independent passages analysing 73–257 cells. *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant.