Claudin-16 affects transcellular Cl(−) secretion in MDCK cells

Claudin-16 (paracellin-1) is a tight junction protein localized mainly in the thick ascending limb of Henle's loop and also in the distal nephron. Its defect causes familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. This had been taken as an indication that claudin-16 conveys pa...

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Main Authors: Günzel, Dorothee, Amasheh, Salah, Pfaffenbach, Sandra, Richter, Jan F, Kausalya, P Jaya, Hunziker, Walter, Fromm, Michael
Format: Artigo
Jezik:English
Izdano: Blackwell Science Inc 2009
Teme:
Molecular and Cellular
Online dostop:https://ncbi.nlm.nih.gov/pmc/articles/PMC2746610/
https://ncbi.nlm.nih.gov/pubmed/19528248
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1113/jphysiol.2009.173401
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spelling pubmed-27466102010-08-01 Claudin-16 affects transcellular Cl(−) secretion in MDCK cells Günzel, Dorothee Amasheh, Salah Pfaffenbach, Sandra Richter, Jan F Kausalya, P Jaya Hunziker, Walter Fromm, Michael J Physiol Molecular and Cellular Claudin-16 (paracellin-1) is a tight junction protein localized mainly in the thick ascending limb of Henle's loop and also in the distal nephron. Its defect causes familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. This had been taken as an indication that claudin-16 conveys paracellular Mg(2+) and Ca(2+) transport; however, evidence is still conflicting. We studied paracellular ion permeabilties as well as effects of claudin-16 on the driving forces for passive ion movement. MDCK-C7 cells were stably transfected with wild-type (wt) and mutant (R146T, T233R) claudin-16. Results indicated that paracellular permeability to Mg(2+) but not to Ca(2+) is increased in cells transfected with wt compared to mutant claudin-16 and control cells. Increased basolateral Mg(2+) concentration activated a transcellular Cl(−) current which was greatly enhanced in cells transfected with wt and T233R claudin-16, as compared to R146T claudin-16-transfected or control cells. This current was triggered by the basolateral calcium-sensing receptor causing Ca(2+) release from internal stores, thus activating apical Ca(2+)-sensitive Cl(−) channels and basolateral Ca(2+)-sensitive K(+) channels. Immunohistochemical data suggest that the Cl(−) channel involved is bestrophin. We conclude that claudin-16 itself possesses only moderate paracellular Mg(2+) permeability but governs transcellular Cl(−) currents by interaction with apical Ca(2+)-activated Cl(−) channels, presumably bestrophin. As the transepithelial voltage generated by such a current alters the driving force for all ions, this may be the major mechanism to regulate Mg(2+) and Ca(2+) absorption in the kidney. Blackwell Science Inc 2009-08-01 2009-06-15 /pmc/articles/PMC2746610/ /pubmed/19528248 http://dx.doi.org/10.1113/jphysiol.2009.173401 Text en Journal compilation © 2009 The Physiological Society
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Molecular and Cellular
spellingShingle Molecular and Cellular
Günzel, Dorothee
Amasheh, Salah
Pfaffenbach, Sandra
Richter, Jan F
Kausalya, P Jaya
Hunziker, Walter
Fromm, Michael
Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
description Claudin-16 (paracellin-1) is a tight junction protein localized mainly in the thick ascending limb of Henle's loop and also in the distal nephron. Its defect causes familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. This had been taken as an indication that claudin-16 conveys paracellular Mg(2+) and Ca(2+) transport; however, evidence is still conflicting. We studied paracellular ion permeabilties as well as effects of claudin-16 on the driving forces for passive ion movement. MDCK-C7 cells were stably transfected with wild-type (wt) and mutant (R146T, T233R) claudin-16. Results indicated that paracellular permeability to Mg(2+) but not to Ca(2+) is increased in cells transfected with wt compared to mutant claudin-16 and control cells. Increased basolateral Mg(2+) concentration activated a transcellular Cl(−) current which was greatly enhanced in cells transfected with wt and T233R claudin-16, as compared to R146T claudin-16-transfected or control cells. This current was triggered by the basolateral calcium-sensing receptor causing Ca(2+) release from internal stores, thus activating apical Ca(2+)-sensitive Cl(−) channels and basolateral Ca(2+)-sensitive K(+) channels. Immunohistochemical data suggest that the Cl(−) channel involved is bestrophin. We conclude that claudin-16 itself possesses only moderate paracellular Mg(2+) permeability but governs transcellular Cl(−) currents by interaction with apical Ca(2+)-activated Cl(−) channels, presumably bestrophin. As the transepithelial voltage generated by such a current alters the driving force for all ions, this may be the major mechanism to regulate Mg(2+) and Ca(2+) absorption in the kidney.
author Günzel, Dorothee
Amasheh, Salah
Pfaffenbach, Sandra
Richter, Jan F
Kausalya, P Jaya
Hunziker, Walter
Fromm, Michael
author_facet Günzel, Dorothee
Amasheh, Salah
Pfaffenbach, Sandra
Richter, Jan F
Kausalya, P Jaya
Hunziker, Walter
Fromm, Michael
author_sort Günzel, Dorothee
title Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
title_short Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
title_full Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
title_fullStr Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
title_full_unstemmed Claudin-16 affects transcellular Cl(−) secretion in MDCK cells
title_sort claudin-16 affects transcellular cl(−) secretion in mdck cells
publisher Blackwell Science Inc
publisher_facet Blackwell Science Inc
publishDate 2009
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2746610/
https://ncbi.nlm.nih.gov/pubmed/19528248
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1113/jphysiol.2009.173401
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