Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1930821 | Biochemical and Biophysical Research Communications | 2011 | 5 Pages |
Nephropathic cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene [1], which encodes for a transporter (cystinosin) responsible for cystine efflux from lysosomes. In cystinotic renal proximal tubules (RPTs), the defect in cystinosin function results in reduced reabsorption of solutes by apical Na+/solute cotransport systems, including the Na+/phosphate (Pi) cotransport system [2]. However the underlying molecular mechanisms are unknown, given the lack of an appropriate cellular model. To obtain such a model system, we have knocked down cystinosin with siRNA in primary RPT cell cultures. An 80% reduction in cystinosin strongly inhibited Na+ dependent Pi uptake (70%). Although this finding could be explained by a direct effect on transporters as well as by altered energetics (the ATP level dropped by 52%), our results demonstrate a lack of involvement of Na, K-ATPase, and a reduction in the number of NaPi2a transporters.
► We examine the effect of a cystinosin knockdown. ► A cystinosin knockdown results in decrease phosphate transport and cellular ATP. ► Decreased phosphate transport can be explained by fewer plasma membrane transporters in cystinosis.