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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Curr+Opin+Nephrol+Hypertens
2016 ; 25
(5
): 424-8
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Paracellular transport in the collecting duct
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Hou J
Curr Opin Nephrol Hypertens
2016[Sep]; 25
(5
): 424-8
PMID27490784
show ga
PURPOSE OF REVIEW: The paracellular pathway through the tight junction provides
an important route for chloride reabsorption in the collecting duct of the
kidney. This review describes recent findings of how defects in paracellular
chloride permeation pathway may cause kidney diseases and how such a pathway may
be regulated to maintain normal chloride homeostasis. RECENT FINDINGS: The tight
junction in the collecting duct expresses two important claudin genes - claudin-4
and claudin-8. Transgenic knockout of either claudin gene causes hypotension,
hypochloremia, and metabolic alkalosis in experimental animals. The claudin-4
mediated chloride permeability can be regulated by a protease endogenously
expressed by the collecting duct cell - channel-activating protease 1.
Channel-activating protease 1 regulates the intercellular interaction of
claudin-4 and its membrane stability. Kelch-like 3, previously identified as a
causal gene for Gordon's syndrome, also known as pseudohypoaldosteronism II,
directly interacts with claudin-8 and regulates its ubiquitination and
degradation. The dominant pseudohypoaldosteronism-II mutation (R528H) in
Kelch-like 3 abolishes claudin-8 binding, ubiquitination, and degradation.
SUMMARY: The paracellular chloride permeation pathway in the kidney is an
important but understudied area in nephrology. It plays vital roles in renal salt
handling and regulation of extracellular fluid volume and blood pressure. Two
claudin proteins, claudin-4 and claudin-8, contribute to the function of this
paracellular pathway. Deletion of either claudin protein from the collecting duct
causes renal chloride reabsorption defects and low blood pressure. Claudins can
be regulated on posttranslational levels by several mechanisms involving protease
and ubiquitin ligase. Deregulation of claudins may cause human hypertension as
exemplified in the Gordon's syndrome.
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