Faculty Opinions recommendation of Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice.

Author(s):  
Kim Barrett
Keyword(s):  
1991 ◽  
Vol 200 (2-3) ◽  
pp. 267-276 ◽  
Author(s):  
Martin Diener ◽  
Cécile Eglème ◽  
Walter Rummel

1992 ◽  
Vol 455 (1) ◽  
pp. 455-469 ◽  
Author(s):  
S J Huang ◽  
A Y Leung ◽  
W O Fu ◽  
Y W Chung ◽  
T S Zhou ◽  
...  

2006 ◽  
Vol 30 (6) ◽  
pp. 547-552 ◽  
Author(s):  
J ZHU ◽  
G ZHANG ◽  
N YANG ◽  
H CONNIEWONG ◽  
Y CHUNG ◽  
...  
Keyword(s):  

2017 ◽  
Vol 312 (6) ◽  
pp. L912-L925 ◽  
Author(s):  
Carol A. Bertrand ◽  
Shalini Mitra ◽  
Sanjay K. Mishra ◽  
Xiaohui Wang ◽  
Yu Zhao ◽  
...  

Several members of the SLC26A family of anion transporters associate with CFTR, forming complexes in which CFTR and SLC26A functions are reciprocally regulated. These associations are thought to be facilitated by PDZ scaffolding interactions. CFTR has been shown to be positively regulated by NHERF-1, and negatively regulated by CAL in airway epithelia. However, it is unclear which PDZ-domain protein(s) interact with SLC26A9, a SLC26A family member found in airway epithelia. We have previously shown that primary, human bronchial epithelia (HBE) from non-CF donors exhibit constitutive anion secretion attributable to SLC26A9. However, constitutive anion secretion is absent in HBE from CF donors. We examined whether changes in SLC26A9 constitutive activity could be attributed to a loss of CFTR trafficking, and what role PDZ interactions played. HEK293 coexpressing SLC26A9 with the trafficking mutant F508del CFTR exhibited a significant reduction in constitutive current compared with cells coexpressing SLC26A9 and wt CFTR. We found that SLC26A9 exhibits complex glycosylation when coexpressed with F508del CFTR, but its expression at the plasma membrane is decreased. SLC26A9 interacted with both NHERF-1 and CAL, and its interaction with both significantly increased with coexpression of wt CFTR. However, coexpression with F508del CFTR only increased SLC26A9’s interaction with CAL. Mutation of SLC26A9’s PDZ motif decreased this association with CAL, and restored its constitutive activity. Correcting aberrant F508del CFTR trafficking in CF HBE with corrector VX-809 also restored SLC26A9 activity. We conclude that when SLC26A9 is coexpressed with F508del CFTR, its trafficking defect leads to a PDZ motif-sensitive intracellular retention of SLC26A9.


1997 ◽  
Vol 8 (8) ◽  
pp. 1222-1231
Author(s):  
G A Tanner ◽  
N Gretz ◽  
Y Shao ◽  
A P Evan ◽  
M Steinhausen

This study examined whether organic anion secretion contributes to fluid accumulation in cysts in polycystic kidney disease. Clearance and micropuncture studies were done on young (7 to 16 wk old), mostly male, heterozygous Han:SPRD cystic rats and healthy control littermate rats. Heterozygous Han:SPRD rats manifest a slowly progressive autosomal dominant polycystic kidney disease that closely resembles the human disorder. Left kidney GFR (polyfructosan clearance), in microl/min per 100 g body wt, averaged 331 +/- 36 (SD) in seven healthy rats and 278 +/- 75 in seven cystic rats. The maximal rate of p-aminohippurate (PAH) secretion, in micromol/min per 100 g body wt, averaged 0.94 +/- 0.24 in healthy rats and 0.83 +/- 0.11 in cystic rats. In these young rats, there were no significant differences in GFR or the maximal rate of PAH secretion despite the presence of cystic disease. Using fluorescence microscopy, it was found that 27 of 29 proximal cysts secreted sulfonefluorescein, an organic anion transported by the PAH system. Transmission electron micrographs of superficial cysts that had secreted sulfonefluorescein demonstrated the presence of both normal-appearing and poorly differentiated proximal tubule cells. Segments of superficial proximal convoluted tubules or cysts, isolated by upstream and downstream wax blocks, failed to accumulate fluid when PAH was infused intravenously. With the stationary microperfusion technique, PAH secretion by both normal and cystic nephrons was demonstrated. It is concluded that most proximal cystic epithelia retain the ability to secrete organic anions. Secretion of organic anions, however, does not appear to contribute in any substantial way to fluid accumulation in cysts in the rat kidney.


2016 ◽  
Vol 594 (12) ◽  
pp. 3339-3352 ◽  
Author(s):  
Izumi Kaji ◽  
Yasutada Akiba ◽  
Kohtarou Konno ◽  
Masahiko Watanabe ◽  
Shunsuke Kimura ◽  
...  

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