ArticleThe Journal of physiology2021
Endocytic adaptation to functional demand by the kidney proximal tubule.
Article in The Journal of physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Renal Functional Reserve-Informed Personalized Renoprotection in Chronic Kidney Disease: A Proposed Extension of the KDIGO CGA Framework.Biomedicines · 2026Review
- Article
- Aberrant activation of renal functional reserve and reduced tubule flow, but not obstruction, is associated with cystogenesis inFunction (Oxford, England) · 2026Article
- Evaluation of the Role of Taurine in Mitigating the Deleterious Effects of Tartrazine on the Kidneys in Rats: Experimental Study.Turk patoloji dergisi · 2026Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Renal handling of albumin in rats with early stage diabetes: A theoretical analysis.The Journal of physiology · 2024Article
- Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome.JCI insight · 2024Article
- The Apical Endocytic-Lysosomal Apparatus in CLCN5 Mutations with Phenotypic-Genotypic Correlations in Three Cases.International journal of molecular sciences · 2024Article
- The pathogenesis of albuminuria in cadmium nephropathy.Current research in toxicology · 2024Article
- Fluid shear stress-induced changes in megalin trafficking enhance endocytic capacity in proximal tubule cells.Frontiers in physiology · 2024Article
- Receptor-associated protein impairs ligand binding to megalin and megalin-dependent endocytic flux in proximal tubule cells.American journal of physiology. Renal physiology · 2023Article
- Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption.Frontiers in pharmacology · 2023Article
- Extended longevity geometrically-inverted proximal tubule organoids.Biomaterials · 2022Article
- Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System.Bioengineering (Basel, Switzerland) · 2022Article
- Modelling normal and nephrotic axial uptake of albumin and other filtered proteins along the proximal tubule.The Journal of physiology · 2022Article
- Assessing proteinuria: value added from a mathematical model.The Journal of physiology · 2022Article
- Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin.International journal of molecular sciences · 2022Article
- An Adaptable Physiological Model of Endocytic Megalin Trafficking in Opossum Kidney Cells and Mouse Kidney Proximal Tubule.Function (Oxford, England) · 2022Article
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Authors and funding
1 author at 1 institution in 1 country.
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Abstract
The kidney proximal tubule (PT) efficiently recovers the low level of albumin and other proteins that normally escape the glomerular filtration barrier. Two large receptors, megalin and cubilin/amnionless (CUBAM), bind to and efficiently retrieve these predominantly low molecular-weight proteins via clathrin-mediated endocytosis. Studies in cell culture models suggest that PT cells may sense changes in shear stress to modulate recovery of filtered proteins in response to normal variations in filtration rate. Impairments in PT endocytic function lead to the excretion of filtered proteins into the urine (tubular proteinuria). Remarkably, when the glomerular filtration barrier is breached, the PT is able to recover excess albumin with a capacity that is orders of magnitude higher than normal. What mediates this excess capacity for albumin uptake under nephrotic conditions, and why doesn't it compensate to prevent tubular proteinuria? Here we propose an integrated new working model to describe the PT recovery of filtered proteins under normal and nephrotic states. We hypothesize that uptake via the fluid phase provides excess capacity to recover high concentrations of filtered proteins under nephrotic conditions. Further, concentration of tubular fluid along the tubule axis will enhance the efficiency of uptake in more distal regions of the PT. By contrast to cells where fluid phase and receptor-mediated uptake are independent pathways, expression of megalin is required to maintain apical endocytic pathway integrity and is essential for both uptake mechanisms. This model accounts for both the high-affinity and the high-capacity responses to filtration load in physiological and pathological states.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.