ArticleAmerican journal of physiology. Renal physiology2010
CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport: relevance to pathophysiology of Dent's disease.
Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
- Gene therapy of Dent disease type 1 in newborn ClC-5 null mice for sustained transgene expression and gene therapy effects.Gene therapy · 2024Article
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- Identification of kinesin family member 3B (KIF3B) as a molecular target for gastric cancer.The Kaohsiung journal of medical sciences · 2020Article
- Research progress on KIF3B and related diseases.Annals of translational medicine · 2019Review
- Single-molecule labeling for studying trafficking of renal transporters.American journal of physiology. Renal physiology · 2018Review
- Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory ClFrontiers in molecular neuroscience · 2018Article
- Receptor-Mediated Endocytosis in the Proximal Tubule.Annual review of physiology · 2017Review
- Overexpression of the Endosomal Anion/Proton Exchanger ClC-5 Increases Cell Susceptibility towardFrontiers in cellular and infection microbiology · 2017Article
- Impaired Lysosomal Function Underlies Monoclonal Light Chain-Associated Renal Fanconi Syndrome.Journal of the American Society of Nephrology : JASN · 2016Article
- Human proximal tubule cells form functional microtissues.Pflugers Archiv : European journal of physiology · 2016Article
- Discovery of CLC transport proteins: cloning, structure, function and pathophysiology.The Journal of physiology · 2015Review
- Chloride transporters and receptor-mediated endocytosis in the renal proximal tubule.The Journal of physiology · 2015Review
- Prolactin stimulates sodium and chloride ion channels in A6 renal epithelial cells.American journal of physiology. Renal physiology · 2015Article
- Endo-lysosomal dysfunction in human proximal tubular epithelial cells deficient for lysosomal cystine transporter cystinosin.PloS one · 2015Article
- The endocytic receptor megalin and its associated proteins in proximal tubule epithelial cells.Membranes · 2014Article
- A patient with nephrotic-range proteinuria and focal global glomerulosclerosis.Clinical journal of the American Society of Nephrology : CJASN · 2013Article
- Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia.The New England journal of medicine · 2013Article
- Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism.Journal of molecular endocrinology · 2013Article
- Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
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.
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