Ca²⁺ signalling in human proximal tubular epithelial cells deficient for cystinosin

Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder caused by loss-of-function mutations in the CTNS gene coding for the lysosomal cystine transporter, cystinosin. Recent studies have demonstrated that, apart from cystine accumulation in the lysosomes, cystinosin-deficient cells, especially renal proximal tubular epithelial cells are characterized by abnormal vesicle trafficking and endocytosis, possible lysosomal dysfunction and perturbed intracellular signalling cascades. It is therefore possible that Ca2+ signalling is disturbed in cystinosis, as it has been demonstrated for other disorders associated with lysosomal dysfunction, such as Gaucher, Niemann-Pick type C and Alzheimer's diseases. In this study we investigated ATP-induced, IP3-induced and lysosomal Ca2+ release in human proximal tubular epithelial cells derived from control and cystinotic patients. No major dysregulation of intracellular Ca2+ dynamics was found, although ATP-induced Ca2+ release appeared slightly sensitized in cystinotic cells compared to control cells. Hence, these subtle changes in Ca2+ signals elicited by agonists may contribute to the pathogenesis of the disease.