دورية أكاديمية
CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease.
| العنوان: | CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease. |
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| المؤلفون: | Reed, Anita A. C., Loh, Nellie Y., Terryn, Sara, Lippiat, Jonathan D., Partridge, Chris, Galvanovskis, Juris, Williams, Sian E., JOURET, François, Wu, Fiona T. F., Courtoy, Pierre J., Nesbit, M. Andrew, Rorsman, Patrik, Devuyst, Olivier, Ashcroft, Frances M., Thakker, Rajesh V. |
| المصدر: | American Journal of Physiology. Renal, Fluid and Electrolyte Physiology, 298 (2), F365-80 (2010) |
| بيانات النشر: | American Physiological Society, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Albumins/metabolism, Animals, COS Cells, Cell Line, Cercopithecus aethiops, Chloride Channels/metabolism/physiology, DNA, Complementary, Down-Regulation, Drug Interactions, Electric Conductivity, Endocytosis/physiology, Gene Library, Genetic Diseases, X-Linked/physiopathology, Humans, Kidney/cytology/metabolism, Kidney Diseases/physiopathology, Kidney Tubules, Proximal/cytology/metabolism, Kinesin/metabolism, Mice, Mice, Knockout, Microtubules/metabolism, Protein Interaction Domains and Motifs, Protein Transport, Two-Hybrid System Techniques, Up-Regulation, Life sciences, Genetics & genetic processes, Sciences du vivant, Génétique & processus génétiques |
| الوصف: | Renal tubular reabsorption is important for extracellular fluid homeostasis and much of this occurs via the receptor-mediated endocytic pathway. This pathway is disrupted in Dent's disease, an X-linked renal tubular disorder that is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Dent's disease is due to mutations of CLC-5, a chloride/proton antiporter, expressed in endosomes and apical membranes of renal tubules. Loss of CLC-5 function alters receptor-mediated endocytosis and trafficking of megalin and cubilin, although the underlying mechanisms remain to be elucidated. Here, we report that CLC-5 interacts with kinesin family member 3B (KIF3B), a heterotrimeric motor protein that facilitates fast anterograde translocation of membranous organelles. Using yeast two-hybrid, glutathione-S-transferase pull-down and coimmunoprecipitation assays, the COOH terminus of CLC-5 and the coiled-coil and globular domains of KIF3B were shown to interact. This was confirmed in vivo by endogenous coimmunoprecipitation of CLC-5 and KIF3B and codistribution with endosomal markers in mouse kidney fractions. Confocal live cell imaging in kidney cells further demonstrated association of CLC-5 and KIF3B, and transport of CLC-5-containing vesicles along KIF3B microtubules. KIF3B overexpression and underexpression, using siRNA, had reciprocal effects on whole cell chloride current amplitudes, CLC-5 cell surface expression, and endocytosis of albumin and transferrin. Clcn5(Y/-) mouse kidneys and isolated proximal tubular polarized cells showed increased KIF3B expression, whose effects on albumin endocytosis were dependent on CLC-5 expression. Thus, the CLC-5 and KIF3B interaction is important for CLC-5 plasma membrane expression and for facilitating endocytosis and microtubular transport in the kidney. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501Test article |
| اللغة: | English |
| العلاقة: | urn:issn:0363-6127; urn:issn:2161-1157 |
| DOI: | 10.1152/ajprenal.00038.2009 |
| الوصول الحر: | https://orbi.uliege.be/handle/2268/134471Test |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2Test info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsorb.134471 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1152/ajprenal.00038.2009 |
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