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

Development ◽  
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.

scholarly journals Characterization of Atp6ap2 ((Pro)‐Renin Receptor) in Receptor Mediated Endocytosis by the Renal Proximal Tubule

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Marta Figueiredo ◽  
Gabin Sihn ◽  
Dominik Müller ◽  
Genevieve Nguyen ◽  
Michael Bader ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Receptor Mediated Endocytosis

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

1985 ◽  
Vol 8 (2) ◽  
pp. 90-99
Author(s):  
Peter D. Ottosen ◽  
Kirsten M. Madsen ◽  
Folkert Bode ◽  
Karl Baumann ◽  
Arvid B. Maunsbach
Keyword(s):  
Amino Acids ◽  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Basic Amino Acids ◽  
Protein Reabsorption

scholarly journals Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

2016 ◽  
Vol 310 (11) ◽  
pp. F1229-F1242 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Gunars Osis ◽  
Mary E. Handlogten ◽  
Wouter H. Lamers ◽  
Farrukh A. Chaudhry ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Glutamine Synthetase ◽  
Proximal Tubule ◽  
Ammonia Excretion ◽  
Renal Proximal Tubule ◽  
Acid Excretion ◽  
Ammonia Metabolism ◽  
Adaptive Changes ◽  
Multiple Components

Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phospho enolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.

The role of IL-7 in renal proximal tubule epithelial cells fibrosis

2012 ◽  
Vol 50 (1-2) ◽  
pp. 74-82 ◽  
Author(s):  
Pei-fang Hsieh ◽  
Shu-Fen Liu ◽  
Tao-Chen Lee ◽  
Jau-Shyang Huang ◽  
Li-Te Yin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Proximal Tubule ◽  
Renal Proximal Tubule

Endocytic Receptors in the Renal Proximal Tubule

Physiology ◽  
2012 ◽  
Vol 27 (4) ◽  
pp. 223-236 ◽  
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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