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Book ; Thesis: Gaining insights in renal magnesium handling

Meij, Iwan Christiaan

2002

Author's details	door Iwan Christiaan Meij
Language	English ; Dutch
Size	128 S. : Ill., graph. Darst.
Publishing country	Netherlands
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Nijmegen, Univ., Diss., 2002
Note	Zsfassung in niederländ. Sprache
HBZ-ID	HT013369697
ISBN	90-915732-8
Database	Catalogue ZB MED Medicine, Health

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Article: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: blocking endocytosis restores surface expression of a novel Claudin-16 mutant that lacks the entire C-terminal cytosolic tail.

Müller, Dominik / Kausalya, P Jaya / Meij, Iwan C / Hunziker, Walter

Human molecular genetics

2006 Volume 15, Issue 7, Page(s) 1049–1058

Abstract: Mutations in the gene for Claudin-16 (CLDN16) are linked to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), a renal Mg2+ and Ca2+ wasting disorder that leads to progressive kidney failure. More than 20 mutations have been ... ...

Abstract	Mutations in the gene for Claudin-16 (CLDN16) are linked to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), a renal Mg2+ and Ca2+ wasting disorder that leads to progressive kidney failure. More than 20 mutations have been identified in CLDN16, which, with a single exception, affect one of two extracellular loops or one of four transmembrane domains of the encoded protein. Here, we describe a novel missense mutation, Cldn16 L203X, which deletes the entire C-terminal cytosolic domain of the protein. Surface expression of Cldn16 L203X is strongly reduced and the protein is instead found in the endoplasmic reticulum (ER) and lysosomes. ER-retained Cldn16 L203X is subject to proteasomal degradation. Cldn16 L203X present in lysosomes reaches this compartment following transport to the plasma membrane and endocytosis. Blocking clathrin-mediated endocytosis increases surface expression of Cldn16 L203X. Thus, endocytosis inhibitors may provide a novel therapeutic approach for FHHNC patients carrying particular Cldn16 mutations.
MeSH term(s)	Amino Acid Sequence ; Animals ; Biological Transport ; Calcium Metabolism Disorders/blood ; Calcium Metabolism Disorders/genetics ; Calcium Metabolism Disorders/metabolism ; Calcium Metabolism Disorders/urine ; Cells, Cultured ; Child, Preschool ; Clathrin/metabolism ; Claudins ; Dogs ; Endocytosis/physiology ; Endoplasmic Reticulum/metabolism ; Fluorescent Antibody Technique ; HeLa Cells ; Homozygote ; Humans ; Kidney/cytology ; Kidney/metabolism ; Lysosomes/metabolism ; Magnesium Deficiency/blood ; Magnesium Deficiency/genetics ; Magnesium Deficiency/metabolism ; Magnesium Deficiency/urine ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Molecular Sequence Data ; Mutation ; Nephrocalcinosis/genetics ; Nephrocalcinosis/metabolism ; Nephrocalcinosis/urine ; Phenotype ; Proteasome Endopeptidase Complex/metabolism ; Transfection
Chemical Substances	Clathrin ; Claudins ; Membrane Proteins ; claudin 16 ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2006-04-01
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddl020
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Article: Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function

Günzel, Dorothee / Stuiver, Marchel / Kausalya, P. Jaya / Haisch, Lea / Krug, Susanne M / Rosenthal, Rita / Meij, Iwan C / Hunziker, Walter / Fromm, Michael / Müller, Dominik

Journal of cell science. 2009 May 15, v. 122, no. 10

2009

Abstract: The tight junction protein claudin-10 is known to exist in two isoforms, resulting from two alternative exons, 1a and 1b (Cldn10a, Cldn10b). Here, we identified and characterized another four claudin-10 splice variants in mouse and human. One (Cldn10a_v1) ...

Abstract	The tight junction protein claudin-10 is known to exist in two isoforms, resulting from two alternative exons, 1a and 1b (Cldn10a, Cldn10b). Here, we identified and characterized another four claudin-10 splice variants in mouse and human. One (Cldn10a_v1) results from an alternative splice donor site, causing a deletion of the last 57 nucleotides of exon 1a. For each of these three variants one further splice variant was identified (Cldn10a_v2, Cldn10a_v3, Cldn10b_v1), lacking exon 4. When transfected into MDCK cells, Cldn10a, Cldn10a_v1 and Cldn10b were inserted into the tight junction, whereas isoforms of splice variants lacking exon 4 were retained in the endoplasmic reticulum. Cldn10a transfection into MDCK cells confirmed the previously described increase in paracellular anion permeability. Cldn10a_v1 transfection had no direct effect, but modulated Cldn10a-induced organic anion permeability. At variance with previous reports in MDCK-II cells, transfection of high-resistance MDCK-C7 cells with Cldn10b dramatically decreased transepithelial resistance, increased cation permeability, and changed monovalent cation selectivity from Eisenman sequence IV to X, indicating the presence of a high field-strength binding site that almost completely removes the hydration shell of the permeating cations. The extent of all these effects strongly depended on the endogenous claudins of the transfected cells.
Language	English
Dates of publication	2009-0515
Size	p. 1507-1517.
Publishing place	The Company of Biologists Limited
Document type	Article
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
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Article ; Online: Membrane topology and intracellular processing of cyclin M2 (CNNM2).

de Baaij, Jeroen H F / Stuiver, Marchel / Meij, Iwan C / Lainez, Sergio / Kopplin, Kathrin / Venselaar, Hanka / Müller, Dominik / Bindels, René J M / Hoenderop, Joost G J

The Journal of biological chemistry

2012 Volume 287, Issue 17, Page(s) 13644–13655

Abstract: Recently, mutations in the cyclin M2 (CNNM2) gene were identified to be causative for severe hypomagnesemia. In kidney, CNNM2 is a basolaterally expressed protein with predominant expression in the distal convoluted tubule. Transcellular magnesium (Mg(2+) ...

Abstract	Recently, mutations in the cyclin M2 (CNNM2) gene were identified to be causative for severe hypomagnesemia. In kidney, CNNM2 is a basolaterally expressed protein with predominant expression in the distal convoluted tubule. Transcellular magnesium (Mg(2+)) reabsorption in the distal convoluted tubule represents the final step before Mg(2+) is excreted into the urine, thus fine-tuning its final excretion via a tightly regulated mechanism. The present study aims to get insight in the structure of CNNM2 and to characterize its post-translational modifications. Here, membrane topology studies using intramolecular epitopes and immunocytochemistry showed that CNNM2 has an extracellular N terminus and an intracellular C terminus. This suggests that one of the predicted transmembrane regions might be re-entrant. By homology modeling, we demonstrated that the loss-of-function mutation as found in patients disturbs the potential ATP binding by the intracellular cystathionine β-synthase domains. In addition, the cellular processing pathway of CNNM2 was exposed in detail. In the endoplasmic reticulum, the signal peptidase complex cleaves off a large N-terminal signal peptide of about 64 amino acids. Mutagenesis screening showed that CNNM2 is glycosylated at residue Asn-112, stabilizing CNNM2 on the plasma membrane. Interestingly, co-immunoprecipitation studies evidenced that CNNM2a forms heterodimers with the smaller isoform CNNM2b. These new findings on CNNM2 structure and processing may aid to elucidate the physiological role of CNNM2 in Mg(2+) reabsorption in the kidney.
MeSH term(s)	Animals ; COS Cells ; Cation Transport Proteins/genetics ; Cell Membrane/metabolism ; Chlorocebus aethiops ; Cyclins/genetics ; Cystathionine beta-Synthase/metabolism ; Endoplasmic Reticulum/metabolism ; Humans ; Immunohistochemistry/methods ; Magnesium/chemistry ; Magnesium/metabolism ; Mice ; Mice, Inbred C57BL ; Mutagenesis ; Mutation ; Protein Isoforms ; Protein Sorting Signals ; Protein Structure, Tertiary ; Tissue Distribution
Chemical Substances	CNNM2 protein, human ; Cation Transport Proteins ; Cnnm2 protein, mouse ; Cyclins ; Protein Isoforms ; Protein Sorting Signals ; Cystathionine beta-Synthase (EC 4.2.1.22) ; Magnesium (I38ZP9992A)
Language	English
Publishing date	2012-03-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M112.342204
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Article ; Online: Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis.

Breiderhoff, Tilman / Himmerkus, Nina / Stuiver, Marchel / Mutig, Kerim / Will, Constanze / Meij, Iwan C / Bachmann, Sebastian / Bleich, Markus / Willnow, Thomas E / Müller, Dominik

Proceedings of the National Academy of Sciences of the United States of America

2012 Volume 109, Issue 35, Page(s) 14241–14246

Abstract: In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes ...

Abstract	In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.
MeSH term(s)	Animals ; Biological Transport/genetics ; Biological Transport/physiology ; Calcium/metabolism ; Claudins/genetics ; Claudins/metabolism ; Drinking/physiology ; Embryonic Stem Cells/physiology ; Gene Deletion ; Homeostasis/genetics ; Homeostasis/physiology ; Loop of Henle/metabolism ; Magnesium/blood ; Metabolic Diseases/genetics ; Metabolic Diseases/metabolism ; Metabolic Diseases/physiopathology ; Mice ; Mice, Knockout ; Nephrocalcinosis/genetics ; Nephrocalcinosis/metabolism ; Nephrocalcinosis/physiopathology ; Phenotype ; Sodium/metabolism ; Water Deprivation/physiology
Chemical Substances	Claudins ; claudin 10 ; Sodium (9NEZ333N27) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1203834109
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Article: Genetic disorders of magnesium homeostasis.

Meij, Iwan C / van den Heuvel, Lambert P W J / Knoers, Nine V A M

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine

2002 Volume 15, Issue 3, Page(s) 297–307

MeSH term(s)	Animals ; Calcium/metabolism ; Homeostasis/genetics ; Humans ; Intestinal Mucosa/metabolism ; Intestines/pathology ; Ion Transport ; Kidney/metabolism ; Kidney/pathology ; Magnesium/metabolism ; Magnesium Deficiency/genetics ; Magnesium Deficiency/metabolism
Chemical Substances	Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2002-08-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1112688-7
ISSN	1572-8773 ; 0966-0844
ISSN (online)	1572-8773
ISSN	0966-0844
DOI	10.1023/a:1016039101747
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Article: Unusual clinical presentation and possible rescue of a novel claudin-16 mutation.

Müller, Dominik / Kausalya, P Jaya / Bockenhauer, Detlef / Thumfart, Julia / Meij, Iwan C / Dillon, Michael J / van't Hoff, William / Hunziker, Walter

The Journal of clinical endocrinology and metabolism

2006 Volume 91, Issue 8, Page(s) 3076–3079

Abstract: Context: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is caused by a dysfunction of Claudin-16 (CLDN16) and characterized by renal wasting of Mg(2+) and Ca(2+).: Objective: The objectives of this study were to study the ... ...

Abstract	Context: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is caused by a dysfunction of Claudin-16 (CLDN16) and characterized by renal wasting of Mg(2+) and Ca(2+). Objective: The objectives of this study were to study the clinical parameters in suspected FHHNC patients, identify mutations in the CLDN16 gene, and analyze molecular defects associated with the mutant protein. Design, setting, and participants: CLDN16 genes from two siblings diagnosed with FHHNC were sequenced. Expression and characterization of the mutant protein in renal MDCK cells were studied. Outcome measures: Standard urine and serum parameters to diagnose FHHNC were determined. Mutations in the CLDN16 gene were identified. The subcellular distribution of the mutant protein was analyzed by immunofluorescence microscopy. Results: Urine and blood analysis showed signs typical for FHHNC. One patient, in addition, presented with hypocalcemic tetany, a phenomenon so far not described for FHHNC. Both siblings carry a novel mutation in CLDN16, Y207X. The review of medical records showed that hypocalcemia is not uncommon in the early childhood of FHHNC patients. Expressed in MDCK cells, the Y207X mutant is not detected at tight junctions but instead is found in lysosomes and, to a lesser extent, the endoplasmic reticulum. Surface expression can be rescued by inhibiting clathrin-mediated internalization. Conclusions: We propose that mutations in CLDN16 are considered in childhood hypocalcemia. CLDN16 Y207X is transiently delivered to the plasma membrane but not retained and is rapidly retrieved by internalization. Inhibitors of endocytosis may provide novel therapeutic strategies.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Calcium/urine ; Cell Line ; Child ; Claudins ; Dogs ; Female ; Fluorescent Antibody Technique ; Gene Expression ; Homozygote ; Humans ; Infant ; Kidney ; Magnesium Deficiency/complications ; Magnesium Deficiency/genetics ; Male ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Microscopy, Fluorescence ; Molecular Sequence Data ; Mutation ; Nephrocalcinosis/complications ; Nephrocalcinosis/genetics ; Sequence Analysis, DNA ; Transfection
Chemical Substances	Claudins ; Membrane Proteins ; claudin 16 ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2006-08
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2006-0200
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Article ; Online: Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting.

Will, Constanze / Breiderhoff, Tilman / Thumfart, Julia / Stuiver, Marchel / Kopplin, Kathrin / Sommer, Kerstin / Günzel, Dorothee / Querfeld, Uwe / Meij, Iwan C / Shan, Qixian / Bleich, Markus / Willnow, Thomas E / Müller, Dominik

American journal of physiology. Renal physiology

2010 Volume 298, Issue 5, Page(s) F1152–61

Abstract: Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of Ca(2+) and Mg(2+) in the thick ascending loop of Henle. To gain novel insights into the role of CLDN16 in renal Ca(2+) and Mg(2+) homeostasis and the pathological mechanisms ... ...

Abstract	Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of Ca(2+) and Mg(2+) in the thick ascending loop of Henle. To gain novel insights into the role of CLDN16 in renal Ca(2+) and Mg(2+) homeostasis and the pathological mechanisms underlying a human disease associated with CLDN16 dysfunction [familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), OMIM 248250], we generated a mouse model of CLDN16 deficiency. Similar to patients, CLDN16-deficient mice displayed hypercalciuria and hypomagnesemia. Contrary to FHHNC patients, nephrocalcinosis was absent in our model, indicating the existence of compensatory pathways in ion handling in this model. In line with the renal loss of Ca(2+), compensatory mechanisms like parathyroid hormone and 1,25(OH)(2)D(3) were significantly elevated. Also, gene expression profiling revealed transcriptional upregulation of several Ca(2+) and Mg(2+) transport systems including Trpv5, Trpm6, and calbindin-D9k. Induced gene expression was also seen for the transcripts of two putative Mg(2+) transport proteins, Cnnm2 and Atp13a4. Moreover, urinary pH was significantly lower when compared with wild-type mice. Taken together, our findings demonstrate that loss of CLDN16 activity leads to specific alterations in Ca(2+) and Mg(2+) homeostasis and that CLDN16-deficient mice represent a useful model to further elucidate pathways involved in renal Ca(2+) and Mg(2+) handling.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Animals ; Biological Transport/physiology ; Calcium/metabolism ; Cation Transport Proteins/metabolism ; Claudins/deficiency ; Claudins/genetics ; Claudins/metabolism ; Disease Models, Animal ; Gene Deletion ; Homeostasis/physiology ; Hypercalciuria/metabolism ; Hypercalciuria/physiopathology ; Magnesium/metabolism ; Membrane Transport Proteins ; Mice ; Mice, Knockout ; Nephrocalcinosis/metabolism ; Nephrocalcinosis/physiopathology ; Renal Tubular Transport, Inborn Errors/metabolism ; Renal Tubular Transport, Inborn Errors/physiopathology ; Signal Transduction/physiology
Chemical Substances	Cation Transport Proteins ; Claudins ; Cnnm2 protein, mouse ; Membrane Transport Proteins ; claudin 16 ; Adenosine Triphosphatases (EC 3.6.1.-) ; ATP13A4 protein, mouse (EC 3.6.1.3) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00499.2009
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Article ; Online: Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation.

Kooij, Gijs / Kopplin, Kathrin / Blasig, Rosel / Stuiver, Marchel / Koning, Nathalie / Goverse, Gera / van der Pol, Susanne M A / van Het Hof, Bert / Gollasch, Maik / Drexhage, Joost A R / Reijerkerk, Arie / Meij, Iwan C / Mebius, Reina / Willnow, Thomas E / Müller, Dominik / Blasig, Ingolf E / de Vries, Helga E

Acta neuropathologica

2014 Volume 128, Issue 2, Page(s) 267–277

Abstract: Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models ... ...

Abstract	Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Animals ; Brain/blood supply ; Brain/pathology ; Brain/physiopathology ; Choroid Plexus/pathology ; Choroid Plexus/physiopathology ; Claudin-3/genetics ; Claudin-3/metabolism ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Encephalomyelitis, Autoimmune, Experimental/physiopathology ; Female ; Humans ; Male ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Microvessels/pathology ; Microvessels/physiopathology ; Middle Aged ; Multiple Sclerosis/pathology ; Multiple Sclerosis/physiopathology ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; Severity of Illness Index
Chemical Substances	CLDN3 protein, human ; Claudin-3 ; Cldn3 protein, mouse ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; myelin oligodendrocyte glycoprotein (35-55)
Language	English
Publishing date	2014-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-013-1227-1
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Article: Claudin-10 exists in six alternatively spliced isoforms that exhibit distinct localization and function.

Günzel, Dorothee / Stuiver, Marchel / Kausalya, P Jaya / Haisch, Lea / Krug, Susanne M / Rosenthal, Rita / Meij, Iwan C / Hunziker, Walter / Fromm, Michael / Müller, Dominik

Journal of cell science

2009 Volume 122, Issue Pt 10, Page(s) 1507–1517

Abstract	The tight junction protein claudin-10 is known to exist in two isoforms, resulting from two alternative exons, 1a and 1b (Cldn10a, Cldn10b). Here, we identified and characterized another four claudin-10 splice variants in mouse and human. One (Cldn10a_v1) results from an alternative splice donor site, causing a deletion of the last 57 nucleotides of exon 1a. For each of these three variants one further splice variant was identified (Cldn10a_v2, Cldn10a_v3, Cldn10b_v1), lacking exon 4. When transfected into MDCK cells, Cldn10a, Cldn10a_v1 and Cldn10b were inserted into the tight junction, whereas isoforms of splice variants lacking exon 4 were retained in the endoplasmic reticulum. Cldn10a transfection into MDCK cells confirmed the previously described increase in paracellular anion permeability. Cldn10a_v1 transfection had no direct effect, but modulated Cldn10a-induced organic anion permeability. At variance with previous reports in MDCK-II cells, transfection of high-resistance MDCK-C7 cells with Cldn10b dramatically decreased transepithelial resistance, increased cation permeability, and changed monovalent cation selectivity from Eisenman sequence IV to X, indicating the presence of a high field-strength binding site that almost completely removes the hydration shell of the permeating cations. The extent of all these effects strongly depended on the endogenous claudins of the transfected cells.
MeSH term(s)	Alternative Splicing ; Animals ; Binding Sites ; Cell Line ; Claudins ; Dogs ; Electric Impedance ; Endoplasmic Reticulum/metabolism ; Exons ; Humans ; Ion Transport ; Kidney/metabolism ; Membrane Potentials ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Permeability ; Phosphoproteins/metabolism ; Protein Conformation ; Protein Isoforms ; Protein Transport ; RNA Splice Sites ; Tight Junctions/metabolism ; Transfection ; Zonula Occludens-1 Protein
Chemical Substances	Claudins ; Membrane Proteins ; Phosphoproteins ; Protein Isoforms ; RNA Splice Sites ; TJP1 protein, human ; Tjp1 protein, mouse ; Zonula Occludens-1 Protein ; claudin 10
Language	English
Publishing date	2009-05-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.040113
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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