Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic adenosine monophosphate dependent, low-conductance chloride channel found on the apical plasma membrane of secretory epithelia. Surprisingly, since cystic fibrosis patients have no kidney phenotype, CFTR is highly expressed in the kidney, present from 12 weeks of gestation in the human metanephric kidney. As well as the mature, full-length, 165-kD wild-type protein (WT-CFTR) associated with renal tubule plasma membranes, intracellular, partially glycosylated forms are also seen in normal kidneys. In addition, a kidney-specific splice variant of CFTR translates a cytoplasmic truncated protein (TNR-CFTR), apparently associated with a specific small endosomal population, and is predominantly expressed in the renal medulla. WT-CFTR and TNR-CFTR show different patterns of developmental regulation, WT-CFTR being the major form expressed early in metanephric development when it is localized at the apical plasma membrane of developing collecting tubules. By contrast, TNR-CFTR expression increases with gestational age, reaching adult levels at 23 weeks. Evidence suggests that WT-CFTR plays a role in chloride secretion into the apical lumen of normal distal tubules. In autosomal dominant polycystic kidney disease, normally targeted CFTR at the apical plasma membrane in association with mislocalized Na-K-ATPase may result in abnormal fluid secretion into cysts. Similar colocalization of WT-CFTR and Na-K-ATPase at the apical plasma membranes is found in collecting tubules during development when it is speculated to play a role in the initiation of opening of the tubule lumen.
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PMID:Cystic fibrosis transmembrane conductance regulator in the kidney: clues to its role? 1045 15

The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in the kidney. CFTR mRNA is detected in all nephron segments of rats and humans and its expression is higher in the renal cortex and outer medulla than in the inner medulla. CFTR protein is detected at the apical surface of both proximal and distal tubules of rat kidney but not in the outer medullary collecting ducts. The localization of CFTR in the proximal tubules is compatible with that of endosomes, suggesting that CFTR might regulate pH in endocytic vesicles by equilibrating H+ accumulation due to H+-ATPase activity. Many studies have also demonstrated that CFTR also regulates channel pore opening and the transport of sodium, chloride and potassium. The kidneys also express a CFTR splicing variant, called TNR-CFTR, in a tissue-specific manner, primarily in the renal medulla. This splicing variant conserves the functional characteristics of wild-type CFTR. The functional significance of TNR-CFTR remains to be elucidated, but our group proposes that TNR-CFTR may have a basic function in intracellular organelles, rather than in the plasma membrane. Also, this splicing variant is able to partially substitute CFTR functions in the renal medulla of Cftr-/- mice and CF patients. In this review we discuss the major functions that have been proposed for CFTR and TNR-CFTR in the kidney.
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PMID:CFTR and TNR-CFTR expression and function in the kidney. 2851 Jan 83