| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Internal
Medicine, Veterans Affairs Medical Center and University of
Michigan School of Medicine, Ann Arbor, Michigan 48105;
3 Department of Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104; and
2 Department of Medical Genetics,
Congenital chloride diarrhea (CLD) is a
recessively inherited disorder characterized by massive loss of
chloride in stool. We previously identified mutations in the
downregulated in adenoma (DRA) gene
in patients with CLD and demonstrated that
DRA encodes an intestine-specific
sulfate transporter. To determine whether DRA is an intestinal chloride
transporter and how mutations affect transport,
Xenopus oocytes were injected with
wild-type and mutagenized DRA cRNA and
uptake of Cl
and
SO24 was assayed. Both
Cl and
SO24 were transported by wild-type DRA and an outwardly directed pH gradient stimulated
Cl uptake, consistent with
Cl/OH
exchange. Among three mutants, C307W transported both anions as
effectively as wild-type, whereas transport activity was lost in
V317del and the double mutant identified in 32 of 32 Finnish CLD
patients. We conclude that DRA is a chloride transporter defective in
CLD and that V317del is a functional mutation and C307W a silent polymorphism.
Xenopus oocytes; intestine; sulfate; genetic disorders
This article has been cited by other articles:
|
|
 |
|
  R. W. Freel, M. Morozumi, and M. Hatch Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1 Am J Physiol Gastrointest Liver Physiol, November 1, 2009; 297(5): G918 - G929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ohana, D. Yang, N. Shcheynikov, and S. Muallem Diverse transport modes by the solute carrier 26 family of anion transporters J. Physiol., May 15, 2009; 587(10): 2179 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Musch, D. L. Arvans, G. D. Wu, and E. B. Chang Functional coupling of the downregulated in adenoma Cl-/base exchanger DRA and the apical Na+/H+ exchangers NHE2 and NHE3 Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G202 - G210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Dorwart, N. Shcheynikov, D. Yang, and S. Muallem The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport Physiology, April 1, 2008; 23(2): 104 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kurita, T. Nakada, A. Kato, H. Doi, A. C. Mistry, M.-H. Chang, M. F. Romero, and S. Hirose Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1402 - R1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Alrefai, X. Wen, W. Jiang, J. P. Katz, K. A. Steinbrecher, M. B. Cohen, I. R. Williams, P. K. Dudeja, and G. D. Wu Molecular cloning and promoter analysis of downregulated in adenoma (DRA) Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G923 - G934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, N. Ameen, J. E. Melvin, and S. Vidyasagar Acute inflammation alters bicarbonate transport in mouse ileum J. Physiol., June 15, 2007; 581(3): 1221 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Simpson, C. W. Schweinfest, G. E. Shull, L. R. Gawenis, N. M. Walker, K. T. Boyle, M. Soleimani, and L. L. Clarke PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1079 - G1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Katoh, M. Tresguerres, K. M. Lee, T. Kaneko, K. Aida, and G. G. Goss Cloning of rainbow trout SLC26A1: involvement in renal sulfate secretion Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1468 - R1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Simpson, L. R. Gawenis, N. M. Walker, K. T. Boyle, and L. L. Clarke Chloride conductance of CFTR facilitates basal Cl-/HCO3- exchange in the villous epithelium of intact murine duodenum Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1241 - G1251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vidyasagar, V. M. Rajendran, and H. J. Binder Three distinct mechanisms of HCO3- secretion in rat distal colon Am J Physiol Cell Physiol, September 1, 2004; 287(3): C612 - C621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Keller, T. Ezaki, R.-J. Guo, and J. P. Lynch Cdx1 or Cdx2 expression activates E-cadherin-mediated cell-cell adhesion and compaction in human COLO 205 cells Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G104 - G114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lohi, G. Lamprecht, D. Markovich, A. Heil, M. Kujala, U. Seidler, and J. Kere Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains Am J Physiol Cell Physiol, March 1, 2003; 284(3): C769 - C779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sterling, N. J. D. Brown, C. T. Supuran, and J. R. Casey The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II Am J Physiol Cell Physiol, November 1, 2002; 283(5): C1522 - C1529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xie, R. Welch, A. Mercado, M. F. Romero, and D. B. Mount Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1 Am J Physiol Renal Physiol, October 1, 2002; 283(4): F826 - F838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saksena, R. K. Gill, I. A. Syed, S. Tyagi, W. A. Alrefai, K. Ramaswamy, and P. K. Dudeja Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G626 - G633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lohi, S. Makela, K. Pulkkinen, P. Hoglund, M.-L. Karjalainen-Lindsberg, P. Puolakkainen, and J. Kere Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G567 - G575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lohi, M. Kujala, S. Makela, E. Lehtonen, M. Kestila, U. Saarialho-Kere, D. Markovich, and J. Kere Functional Characterization of Three Novel Tissue-specific Anion Exchangers SLC26A7, -A8, and -A9 J. Biol. Chem., April 12, 2002; 277(16): 14246 - 14254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Markovich Physiological Roles and Regulation of Mammalian Sulfate Transporters Physiol Rev, October 1, 2001; 81(4): 1499 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Hoglund, C Holmberg, P Sherman, and J Kere Distinct outcomes of chloride diarrhoea in two siblings with identical genetic background of the disease: implications for early diagnosis and treatment Gut, May 1, 2001; 48(5): 724 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Rajendran, J. Black, T. A. Ardito, P. Sangan, S. L. Alper, C. Schweinfest, M. Kashgarian, and H. J. Binder Regulation of DRA and AE1 in rat colon by dietary Na depletion Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G931 - G942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Melvin, K. Park, L. Richardson, P. J. Schultheis, and G. E. Shull Mouse Down-regulated in Adenoma (DRA) Is an Intestinal Cl-/HCO3- Exchanger and Is Up-regulated in Colon of Mice Lacking the NHE3 Na+/H+ Exchanger J. Biol. Chem., August 6, 1999; 274(32): 22855 - 22861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kere, H. Lohi, and P. Hoglund III. Congenital chloride diarrhea Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G7 - G13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mercado, L. Song, N. Vazquez, D. B. Mount, and G. Gamba Functional Comparison of the K+-Cl- Cotransporters KCC1 and KCC4 J. Biol. Chem., September 22, 2000; 275(39): 30326 - 30334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Toure, L. Morin, C. Pineau, F. Becq, O. Dorseuil, and G. Gacon Tat1, a Novel Sulfate Transporter Specifically Expressed in Human Male Germ Cells and Potentially Linked to RhoGTPase Signaling J. Biol. Chem., June 1, 2001; 276(23): 20309 - 20315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
