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rdf:type |
|
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lifeskim:mentions |
umls-concept:C0014139,
umls-concept:C0017262,
umls-concept:C0020438,
umls-concept:C0027709,
umls-concept:C0039259,
umls-concept:C0151723,
umls-concept:C0185117,
umls-concept:C0205148,
umls-concept:C0205314,
umls-concept:C0241888,
umls-concept:C0332206,
umls-concept:C0439751,
umls-concept:C0596988,
umls-concept:C0679622,
umls-concept:C1142723,
umls-concept:C1383501,
umls-concept:C1707271,
umls-concept:C2911684
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|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2006-3-15
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|
pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0964-6906
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pubmed:author |
|
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
15
|
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1049-58
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16501001-Amino Acid Sequence,
pubmed-meshheading:16501001-Animals,
pubmed-meshheading:16501001-Biological Transport,
pubmed-meshheading:16501001-Calcium Metabolism Disorders,
pubmed-meshheading:16501001-Cells, Cultured,
pubmed-meshheading:16501001-Child, Preschool,
pubmed-meshheading:16501001-Clathrin,
pubmed-meshheading:16501001-Dogs,
pubmed-meshheading:16501001-Endocytosis,
pubmed-meshheading:16501001-Endoplasmic Reticulum,
pubmed-meshheading:16501001-Fluorescent Antibody Technique,
pubmed-meshheading:16501001-HeLa Cells,
pubmed-meshheading:16501001-Homozygote,
pubmed-meshheading:16501001-Humans,
pubmed-meshheading:16501001-Kidney,
pubmed-meshheading:16501001-Lysosomes,
pubmed-meshheading:16501001-Magnesium Deficiency,
pubmed-meshheading:16501001-Membrane Proteins,
pubmed-meshheading:16501001-Molecular Sequence Data,
pubmed-meshheading:16501001-Mutation,
pubmed-meshheading:16501001-Nephrocalcinosis,
pubmed-meshheading:16501001-Phenotype,
pubmed-meshheading:16501001-Proteasome Endopeptidase Complex,
pubmed-meshheading:16501001-Transfection
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pubmed:year |
2006
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Department of Pediatric Nephrology and Center for Cardiovascular Research, Charité, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
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