ArticleProceedings of the National Academy of Sciences of the United States of America2014
Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 148 citations in OpenAlex.
- Primary cilium as a sensory organelle and metabolic hub in health and diseases.Journal of biomedical science · 2026Review
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Aberrant activation of renal functional reserve and reduced tubule flow, but not obstruction, is associated with cystogenesis inFunction (Oxford, England) · 2026Article
- Microphysiological Systems for Comorbidity Studies: Chronic Kidney Disease and Osteoarthritis.Advanced healthcare materials · 2025Review
- Decellularized rat tubules for tissue engineering.Translational andrology and urology · 2025Article
- Flow-induced mechano-modulation of intestinal permeability on chip.Materials today. Bio · 2025Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Modelling Lowe syndrome and Dent-2 disease using zebrafish.Frontiers in cell and developmental biology · 2025Review
- Shear stress effects on epididymal epithelial cell via primary cilia mechanosensory signaling.Journal of cellular physiology · 2025Article
- Quantitative Intravital Calcium Imaging in Mouse Kidney.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Highly scalable and standardized organ-on-chip platform with TEER for biological barrier modeling.Tissue barriers · 2024Article
- Renal handling of albumin in rats with early stage diabetes: A theoretical analysis.The Journal of physiology · 2024Article
- SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.American journal of physiology. Renal physiology · 2024Article
- Enhanced solute transport and steady mechanical stimulation in a novel dynamic perifusion bioreactor increase the efficiency of theFrontiers in bioengineering and biotechnology · 2024Article
- The shear rate promotes pinocytosis of extracellular dextran in platelets.Clinical hemorheology and microcirculation · 2024Article
- ROCK inhibition enhanced hepatocyte liver engraftment by retaining membrane CD59 and attenuating complement activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Megalin, cubilin, and Dab2 drive endocytic flux in kidney proximal tubule cells.Molecular biology of the cell · 2023Article
- Scanning electron microscopy of human islet cilia.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Shear stress regulation of nanoparticle uptake in vascular endothelial cells.Regenerative biomaterials · 2023Review
- Effect of mechanical forces on cellular response to radiation.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The kidney has an extraordinary ability to maintain stable fractional solute and fluid reabsorption over a wide range of glomerular filtration rates (GFRs). Internalization of filtered low molecular weight proteins, vitamins, hormones, and other small molecules is mediated by the proximal tubule (PT) multiligand receptors megalin and cubilin. Changes in GFR and the accompanying fluid shear stress (FSS) modulate acute changes in PT ion transport thought to be mediated by microvillar bending. We found that FSS also affects apical endocytosis in PT cells. Exposure of immortalized PT cell lines to physiologically relevant levels of FSS led to dramatically increased internalization of the megalin-cubilin ligand albumin as well as the fluid phase marker dextran. FSS-stimulated apical endocytosis was initiated between 15 and 30 min postinduction of FSS, occurred via a clathrin- and dynamin-dependent pathway, and was rapidly reversed upon removing the FSS. Exposure to FSS also caused a rapid elevation in intracellular Ca(2+) [Ca(2+)]i, which was not observed in deciliated cells, upon treatment with BAPTA-AM, or upon inclusion of apyrase in the perfusion medium. Strikingly, deciliation, BAPTA-AM, and apyrase also blocked the flow-dependent increase in endocytosis. Moreover, addition of ATP bypassed the need for FSS in enhancing endocytic capacity. Our studies suggest that increased [Ca(2+)]i and purinergic signaling in response to FSS-dependent ciliary bending triggers a rapid and reversible increase in apical endocytosis that contributes to the efficient retrieval of filtered proteins in the PT.
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