Endoplasmic reticulum and lysosomal Ca²⁺ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts

Cell Calcium. 2016 Jan;59(1):12-20. doi: 10.1016/j.ceca.2015.11.002. Epub 2015 Nov 26.


Mutations in β-glucocerebrosidase (encoded by GBA1) cause Gaucher disease (GD), a lysosomal storage disorder, and increase the risk of developing Parkinson disease (PD). The pathogenetic relationship between the two disorders is unclear. Here, we characterised Ca(2+) release in fibroblasts from type I GD and PD patients together with age-matched, asymptomatic carriers, all with the common N370S mutation in β-glucocerebrosidase. We show that endoplasmic reticulum (ER) Ca(2+) release was potentiated in GD and PD patient fibroblasts but not in cells from asymptomatic carriers. ER Ca(2+) signalling was also potentiated in fibroblasts from aged healthy subjects relative to younger individuals but not further increased in aged PD patient cells. Chemical or molecular inhibition of β-glucocerebrosidase in fibroblasts and a neuronal cell line did not affect ER Ca(2+) signalling suggesting defects are independent of enzymatic activity loss. Conversely, lysosomal Ca(2+) store content was reduced in PD fibroblasts and associated with age-dependent alterations in lysosomal morphology. Accelerated remodelling of Ca(2+) stores by pathogenic GBA1 mutations may therefore feature in PD.

Keywords: Ca(2+); Endoplasmic reticulum; Gaucher disease; Lysosomes; Parkinson disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / pathology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Glucosylceramidase / metabolism*
  • Humans
  • Lysosomes / metabolism*
  • Lysosomes / pathology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology


  • Glucosylceramidase
  • Calcium