Inhibition of Protein Reabsorption in the Renal Proximal Tubule by Basic Amino Acids

Peter D. Ottosen; Kirsten M. Madsen; Folkert Bode; Karl Baumann; Arvid B. Maunsbach

doi:10.1159/000173040

Long-term protein exposure reduces albumin binding and uptake in proximal tubule-derived opossum kidney cells.

Journal of the American Society of Nephrology ◽

10.1681/asn.v96960 ◽

1998 ◽

Vol 9 (6) ◽

pp. 960-968 ◽

Cited By ~ 1

Author(s):

M Gekle ◽

S Mildenberger ◽

R Freudinger ◽

S Silbernagl

Keyword(s):

Amino Acids ◽

Proximal Tubule ◽

Uptake Rate ◽

Kidney Cells ◽

Proximal Tubular Cells ◽

Opossum Kidney ◽

Tubular Cells ◽

Opossum Kidney Cells ◽

Proximal Tubular ◽

Protein Reabsorption

To avoid renal loss of large amounts of proteins, filtered proteins are reabsorbed by endocytosis along the proximal tubule. However, although protein reabsorption is a task of proximal tubular cells, it is also a threat because it may cause cell injury. This study determines whether exposure to bovine serum albumin (BSA) leads to regulatory changes in endocytosis of FITC-BSA in proximal tubule-derived opossum kidney cells. Preincubation with BSA led to a decrease of FITC-BSA endocytosis with an IC50 value of 0.58 g/L. Specific binding of FITC-BSA to the apical membrane was also reduced (IC50 = 0.69 g/L). Kinetic analyses revealed that maximal uptake rate and maximal binding capacity were decreased with no change in affinity. Similar effects were observed after preincubation with equimolar amounts of other proteins (lactalbumin, transferrin, and conalbumin), but not after preincubation with dextran. The effect of preincubation with BSA could be mimicked by preincubation with some amino acids. Preincubation with L-Ala, L-Gln, or NH4Cl, but not with L-Leu, L-Glu, or L-Asp, reduced FITC-BSA endocytosis and binding. Preincubation with BSA, but not with dextran, reduced protein degradation and increased ammonia production, vesicular pH, as well as the rate of lactate dehydrogenase release. Apical fluid-phase endocytosis and apical uptake of neutral amino acids were not reduced. It is concluded that proximal tubular cells reduce the uptake rate for proteins, but not for other substrates, in response to increased protein load. This reduction is achieved by reducing the number of apical binding sites, partially in response to increased ammoniagenesis with deranged vesicular pH and enzyme activities. Thus, increased protein filtration could result in reduced protein reabsorption, thereby enhancing proteinuria.

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Endocytic Receptors in the Renal Proximal Tubule

Physiology ◽

10.1152/physiol.00022.2012 ◽

2012 ◽

Vol 27 (4) ◽

pp. 223-236 ◽

Cited By ~ 121

Author(s):

Erik I. Christensen ◽

Henrik Birn ◽

Tina Storm ◽

Kathrin Weyer ◽

Rikke Nielsen

Keyword(s):

Molecular Biology ◽

Proximal Tubule ◽

Plasma Proteins ◽

Animal Studies ◽

Renal Proximal Tubule ◽

Protein Clearance ◽

Pathological Conditions ◽

Protein Reabsorption

Protein reabsorption is a predominant feature of the renal proximal tubule. Animal studies show that the ability to rescue plasma proteins relies on the endocytic receptors megalin and cubilin. Recently, studies of patients with syndromes caused by dysfunctional receptors have supported the importance of these for protein clearance of human ultrafiltrate. This review focuses on the molecular biology and physiology of the receptors and their involvement in renal pathological conditions.

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Protein reabsorption in renal proximal tubule?function and dysfunction in kidney pathophysiology

Pediatric Nephrology ◽

10.1007/s00467-004-1494-0 ◽

2004 ◽

Vol 19 (7) ◽

pp. 714-721 ◽

Cited By ~ 96

Author(s):

Erik I. Christensen ◽

Jakub Gburek

Keyword(s):

Proximal Tubule ◽

Renal Proximal Tubule ◽

Protein Reabsorption

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Endocytosis mediated by an atypical CUBAM complex modulates slit diaphragm dynamics in nephrocytes

Development ◽

10.1242/dev.199894 ◽

2021 ◽

Author(s):

Alexandra Atienza-Manuel ◽

Vicente Castillo-Mancho ◽

Stefano De Renzis ◽

Joaquim Culi ◽

Mar Ruiz-Gómez

Keyword(s):

Proximal Tubule ◽

Morphological Changes ◽

Renal Proximal Tubule ◽

Slit Diaphragm ◽

Specific Requirement ◽

Receptor Mediated Endocytosis ◽

Highly Active ◽

Protein Reabsorption

The vertebrate endocytic receptor CUBAM, consisting of three cubilin monomers complexed with a single amnionless molecule, plays a major role in protein reabsorption in the renal proximal tubule. Here, we show that Drosophila CUBAM is a tripartite complex composed of dAmnionless and two cubilin paralogues Cubilin and Cubilin-2, and that it is required for nephrocyte slit diaphragm (SD) dynamics. Loss of CUBAM-mediated endocytosis induces dramatic morphological changes in nephrocytes and promotes enlarged ingressions of the external membrane and SD mislocalisation. These phenotypes result in part from an imbalance between endocytosis, strongly impaired in CUBAM mutants, and exocytosis in these highly active cells. Noteworthy, rescuing receptor-mediated endocytosis by Megalin/LRP2 or Rab5 expression only partially restores SD-positioning in CUBAM mutants, suggesting a specific requirement of CUBAM in SD degradation and/or recycling. This finding and the reported expression of CUBAM in podocytes argue for a possible unexpected conserved role of this endocytic receptor in vertebrate SD remodelling.

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The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100073544 ◽

1973 ◽

Vol 31 ◽

pp. 620-621

Author(s):

J. M. Barrett ◽

P. M. Heidger

Keyword(s):

Fine Structure ◽

Proximal Tubule ◽

Rat Kidney ◽

Renal Proximal Tubule ◽

Convincing Evidence ◽

Cytoplasmic Bodies ◽

Rat Renal Proximal Tubule ◽

Renal Proximal Tubule Cells ◽

Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

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