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Am J Physiol Renal Physiol 270: F1038-F1048, 1996;
0363-6127/96 $5.00
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AJP - Renal Physiology, Vol 270, Issue 6 1038-F1048, Copyright © 1996 by American Physiological Society

ARTICLES

Both the wild type and a functional isoform of CFTR are expressed in kidney

M. M. Morales, T. P. Carroll, T. Morita, E. M. Schwiebert, O. Devuyst, P. D. Wilson, A. G. Lopes, B. A. Stanton, H. C. Dietz, G. R. Cutting and W. B. Guggino
Department of Physiology, Johns Hopkins University School of Medicine Baltimore, Maryland 21205, USA.

The cystic fibrosis transmembrane conductance regulator (CFTR) consists of five domains, two transmembrane-spanning domains, each composed of six transmembrane segments, a regulatory domain, and two nucleotide-binding domains (NBDs). CFTR is expressed in kidney, but its role in overall renal function is not well understood, because mutations in CFTR found in patients with cystic fibrosis are not associated with renal dysfunction. To learn more about the distribution and functional forms of CFTR in kidney, we used a combination of molecular, cell biological, and electrophysiological approaches. These include an evaluation of CFTR mRNA and protein expression, as well as both two-electrode and patch clamping of CFTR expressed either in Xenopus oocytes or mammalian cells. In addition to wild-type CFTR mRNA, an alternate form containing only the first transmembrane domain (TMD), the first NBD, and the regulatory domain (TNR-CFTR) is expressed in kidney. Although missing the second set of TMDs and the second NBD, when expressed in Xenopus oocytes, TNR-CFTR has cAMP-dependent protein kinase A (PKA)-stimulated single Cl- channel characteristics and regulation of PKA activation of outwardly rectifying Cl- channels that are very similar to those of wild-type CFTR. TNR-CFTR mRNA is produced by an unusual mRNA processing mechanism and is expressed in a tissue-specific manner primarily in renal medulla.


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