ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease

Piwon N, Günther W, Schwake M, Bösl MR, Jentsch TJ (2000)
Nature 408(6810): 369-373.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Piwon, Nils; Günther, Willy; Schwake, MichaelUniBi ; Bösl, Michael R.; Jentsch, Thomas J.
Abstract / Bemerkung
Dent's disease is an X-linked disorder associated with the urinary loss of low-molecular-weight proteins, phosphate and calcium, which often leads to kidney stones1,2. It is caused by mutations3 in ClC-5, a renal chloride channel4,5 that is expressed in endosomes of the proximal tubule6,7. Here we show that disruption of the mouse clcn5 gene causes proteinuria by strongly reducing apical proximal tubular endocytosis. Both receptor-mediated and fluid-phase endocytosis are affected, and the internalization of the apical transporters NaPi-2 and NHE3 is slowed. At steady state, however, both proteins are redistributed from the plasma membrane to intracellular vesicles. This may be caused by an increased stimulation of luminal parathyroid hormone (PTH) receptors owing to the observed decreased tubular endocytosis of PTH. The rise in luminal PTH concentration should also stimulate the hydroxylation of 25(OH) vitamin D3 to the active hormone. However, this is counteracted by a urinary loss of the precursor 25(OH) vitamin D3. The balance between these opposing effects, both of which are secondary to the defect in proximal tubular endocytosis, probably determines whether there will be hypercalciuria and kidney stones.
Erscheinungsjahr
2000
Zeitschriftentitel
Nature
Band
408
Ausgabe
6810
Seite(n)
369-373
ISSN
0028-0836
eISSN
1476-4687
Page URI
https://pub.uni-bielefeld.de/record/2953364

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Piwon N, Günther W, Schwake M, Bösl MR, Jentsch TJ. ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature. 2000;408(6810):369-373.
Piwon, N., Günther, W., Schwake, M., Bösl, M. R., & Jentsch, T. J. (2000). ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature, 408(6810), 369-373. https://doi.org/10.1038/35042597
Piwon, N., Günther, W., Schwake, M., Bösl, M. R., and Jentsch, T. J. (2000). ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 408, 369-373.
Piwon, N., et al., 2000. ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature, 408(6810), p 369-373.
N. Piwon, et al., “ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease”, Nature, vol. 408, 2000, pp. 369-373.
Piwon, N., Günther, W., Schwake, M., Bösl, M.R., Jentsch, T.J.: ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature. 408, 369-373 (2000).
Piwon, Nils, Günther, Willy, Schwake, Michael, Bösl, Michael R., and Jentsch, Thomas J. “ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease”. Nature 408.6810 (2000): 369-373.

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