Academic Journal
Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules.
| العنوان: | Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. |
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| المؤلفون: | Christensen, Erik I, Devuyst, Olivier, Dom, Geneviève, Nielsen, Rikke, Van der Smissen, Patrick, Verroust, Pierre, Leruth, Michèle, Guggino, William B, Courtoy, Pierre Joseph |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America, 100 (14 |
| سنة النشر: | 2003 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Sciences bio-médicales et agricoles, Absorption, Animals, Blood Proteins -- metabolism, Cell Polarity, Chloride Channels -- deficiency -- genetics -- physiology, Endocytosis, Endosomes -- metabolism, Fanconi Syndrome -- metabolism, Hydrogen-Ion Concentration, Immunohistochemistry, Ion Transport, Kidney Tubules, Proximal -- metabolism -- ultrastructure, Ligands, Low Density Lipoprotein Receptor-Related Protein-2 -- genetics -- metabolism, Male, Mice, Knockout, Microvilli -- metabolism, Protein Transport, RNA, Messenger -- biosynthesis, Receptors, Cell Surface -- genetics -- metabolism, rab GTP-Binding Proteins -- metabolism, rab5 GTP-Binding Proteins -- metabolism |
| الوصف: | Loss of the renal endosome-associated chloride channel, ClC-5, in Dent's disease and knockout (KO) mice strongly inhibits endocytosis of filtered proteins by kidney proximal tubular cells (PTC). The underlying mechanism remains unknown. We therefore tested whether this endocytic failure could primarily reflect a loss of reabsorption by the multiligand receptors, megalin, and cubilin, caused by a trafficking defect. Impaired protein endocytosis in PTC of ClC-5 KO mice was demonstrated by (i) a major decreased uptake of injected 125I-beta 2-microglobulin, but not of the fluid-phase tracer, FITC-dextran, (ii) reduced labeling of endosomes by injected peroxidase and for the endogenous megalin/cubilin ligands, vitamin D- and retinol-binding proteins, and (iii) urinary appearance of low-molecular-weight proteins and the selective cubilin ligand, transferrin. Contrasting with preserved mRNA levels, megalin and cubilin abundance was significantly decreased in kidney extracts of KO mice. Percoll gradients resolving early and late endosomes (Rab5a, Rab7), brush border (villin, aminopeptidase M), and a dense peak comprising lysosomes (acid hydrolases) showed a disappearance of the brush border component for megalin and cubilin in KO mice. Quantitative ultrastructural immunogold labeling confirmed the overall decrease of megalin and cubilin in PTC and their selective loss at the brush border. In contrast, total contents of the rate-limiting endocytic catalysts, Rab5a and Rab7, were unaffected. Thus, impaired protein endocytosis caused by invalidation of ClC-5 primarily reflects a trafficking defect of megalin and cubilin in PTC. ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| Relation: | uri/info:doi/10.1073/pnas.1432873100; uri/info:pii/1432873100; uri/info:pmid/12815097; uri/info:pmcid/PMC166253; https://dipot.ulb.ac.be/dspace/bitstream/2013/269026/4/PMC166253.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/269026 |
| الاتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/269026 https://dipot.ulb.ac.be/dspace/bitstream/2013/269026/4/PMC166253.pdf |
| رقم الانضمام: | edsbas.FF7CD6AC |
| قاعدة البيانات: | BASE |
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