ABCMdb

ABCC7 p.Cys590*

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Publications
[hide] The first-nucleotide binding domain of the cystic-... Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5310-5. Schreiber R, Hopf A, Mall M, Greger R, Kunzelmann K
The first-nucleotide binding domain of the cystic-fibrosis transmembrane conductance regulator is important for inhibition of the epithelial Na+ channel.
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5310-5., 1999-04-27 [PMID:10220462]

Abstract [show]
The cystic-fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-regulated Cl- channel and as a regulator of other membrane conductances. cAMP-dependent activation of CFTR inhibits epithelial Na+ channels (ENaC). The specificity of interaction between CFTR and ENaC was examined by coexpression of ENaC and ATP-binding cassette (ABC) proteins other than CFTR. In addition, we identified domains within CFTR that are of particular importance for the inhibition of ENaC. To that end, two-electrode voltage-clamp experiments were performed on Xenopus oocytes coexpressing ENaC together with CFTR, the multidrug resistance protein MDR1, the sulfonyl urea receptor SUR1, or the cadmium permease YCF1. Except for CFTR, none of the other ABC proteins were able to inhibit ENaC. Several truncated versions of CFTR were examined for their inhibitory effects on ENaC. In fact, it is shown that C-terminal truncated CFTR is able to inhibit ENaC on activation by intracellular cAMP. Moreover, the data also show that an intact first-nucleotide binding domain (NBF-1) is important for inhibition of ENaC. We conclude that NBF-1 of CFTR contains a CFTR-specific regulatory site that down-regulates ENaC. It is speculated that this regulatory site also is needed for CFTR-mediated interactions with other membrane proteins and that it is not present in NBF-1 of other ABC proteins.

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Sentences [show]
No. Sentence Comment
44 5310 terminal CFTR truncation including the N terminus, the first six transmembrane helices, and NBF-1 (C590X) was obtained as a SpeI͞KpnI CFTR cDNA fragment. Login to comment
97 Several truncated versions of CFTR were generated to identify CFTR domains essential to the down-regulation of ENaC: (i) the central cytosolic part of CFTR including two transmembrane helices on each site (M284͞I942X); (ii) NBF-1 (W401M͞D651X); (iii) the N-terminal half of CFTR without NBF-1 (E402X); (iv) the N-terminal half of CFTR including NBF-1 (C590X); (v) the N-terminal half of CFTR including an additional stretch of 61 amino acids, as described in a recent study (ref. 17; D651X); (vi) the N-terminal half of CFTR including NBF-1 and the R domain (E831X); and (vii) the C-terminal half including the R domain but not NBF-1 (M595-C). Login to comment
117 As shown as an example in Fig. 6A, the N-terminal half of CFTR without the R domain (C590X) is able to inhibit ENaC. Login to comment
128 FIG. 6. Time course of the whole-cell conductance measured in oocytes coexpressing C590X and ␣-, beta-, and ␥-ENaC (A) or M595-C and ␣-, beta-, and ␥-ENaC (B). Login to comment
129 Amiloride (Amil; 10 ␮mol͞liter) blocked most of the whole-cell conductance when applied under control conditions. In C590X-expressing oocytes, whole-cell conductances were inhibited, and the effect of amiloride was attenuated after stimulation with IBMX and forskolin. Login to comment

[hide] Aquaporin 3 cloned from Xenopus laevis is regulate... FEBS Lett. 2000 Jun 23;475(3):291-5. Schreiber R, Pavenstadt H, Greger R, Kunzelmann K
Aquaporin 3 cloned from Xenopus laevis is regulated by the cystic fibrosis transmembrane conductance regulator.
FEBS Lett. 2000 Jun 23;475(3):291-5., [PMID:10869574]

Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) is essential for epithelial electrolyte transport and has been shown to be a regulator of epithelial Na(+), K(+), and Cl(-) channels. CFTR also enhances osmotic water permeability when activated by cAMP. This was detected initially in Xenopus oocytes and is also present in human airway epithelial cells, however, the mechanisms remain obscure. Here, we show that CFTR activates aquaporin 3 expressed endogenously and exogenously in oocytes of Xenopus laevis. The interaction requires stimulation of wild type CFTR by cAMP and an intact first nucleotide binding domain as demonstrated for other CFTR-protein interactions.

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Sentences [show]
No. Sentence Comment
46 Oocytes of identical batches were injected with 20 ng cRNA of wild type (wt) CFTR, G551D-CFTR, xAQP3 and truncated forms of CFTR: M595-C (C-terminal half of CFTR including R-domain but not NBD1); C590X (N-terminal half of CFTR including N-terminus, the 'rst six transmembrane helices and NBD1 but not R-domain); M394-K830 (NBD1 and R-domain); W401M-D651X (NBD1 only). Login to comment
139 After stimulation Pgly was enhanced in wtCFTR, C590X and W410M-D651X expressing oocytes but not in oocytes injected with the C-terminal half of CFTR (M595-C). Login to comment