Fig. 4.

Pathogenic LRRK2 disrupts local and global Ca²⁺ signalling. (A–D) LAMP1 staining in fibroblasts from a healthy control (CTRL) (A) and a Parkinson disease patient (PD) (B–D) treated for 2 h with either DMSO (A,B) or 10 µM acetoxymethyl (AM) esters of the Ca²⁺ chelators BAPTA (C) or EGTA (D). Scale bars: 5 µm. (E) Pooled data quantifying LAMP1 intensity for the cells shown in A–D (mean±s.e.m., n = 150–307 cells from six independent platings of two patient and paired controls). ***P<0.001. (F,G) Cytosolic Ca²⁺ responses of individual Fura-2-loaded healthy (F) or Parkinson disease (G) fibroblasts microinjected with either vehicle (blue traces) or NAADP (20 µM pipette; black traces). (H) Pooled data (n = 6) quantifying the change in ratio upon microinjection of NAADP (left) or vehicle (right).