title: Ca(2+) signalling in human proximal tubular epithelial cells deficient for cystinosin.
abstract: 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.
authors.affiliation: KU Leuven and UZ Leuven, Department of Pediatric Nephrology & Growth and Regeneration, Leuven, Belgium.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Ivanova
authors.affiliation: KU Leuven and UZ Leuven, Department of Pediatric Nephrology & Growth and Regeneration, Leuven, Belgium; Cairo University, Faculty of Medicine, Department of Clinical and Chemical Pathology, Cairo, Egypt. Electronic address: mohamed.ibrahim@kuleuven.be.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Elmonem
authors.affiliation: KU Leuven and UZ Leuven, Department of Pediatric Nephrology & Growth and Regeneration, Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Bongaerts
authors.affiliation: KU Leuven, Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, Leuven, Belgium.
authors.forename: Tomas
authors.initials: T
authors.lastname: Luyten
authors.affiliation: KU Leuven, Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, Leuven, Belgium.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Missiaen
authors.affiliation: KU Leuven and UZ Leuven, Department of Pediatric Nephrology & Growth and Regeneration, Leuven, Belgium; Radboud University Medical Center, Department of Pediatric Nephrology, Nijmegen, The Netherlands.
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.affiliation: KU Leuven and UZ Leuven, Department of Pediatric Nephrology & Growth and Regeneration, Leuven, Belgium.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Levtchenko
authors.affiliation: KU Leuven, Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D003554:Cystinosis / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D002118:Calcium
keywords: Calcium homeostasis; Lysosomal storage disorders; Nephropathic cystinosis