Ca(2+) signalling in human proximal tubular epithelial cells deficient for cystinosin.

Ivanova, E. A., M. A. Elmonem, I. Bongaerts, T. Luyten, L. Missiaen, L. P. van den Heuvel, E. N. Levtchenko, and G. Bultynck, "Ca(2+) signalling in human proximal tubular epithelial cells deficient for cystinosin.", Cell calcium, vol. 60, issue 4, pp. 282-7, 2016 Oct.


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 Ca(2+) 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 Ca(2+) release in human proximal tubular epithelial cells derived from control and cystinotic patients. No major dysregulation of intracellular Ca(2+) dynamics was found, although ATP-induced Ca(2+) release appeared slightly sensitized in cystinotic cells compared to control cells. Hence, these subtle changes in Ca(2+) signals elicited by agonists may contribute to the pathogenesis of the disease.