Chloride transporters and receptor-mediated endocytosis in the renal proximal tubule

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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Faculty Opinions recommendation of Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1119212.575374 ◽

2008 ◽

Author(s):

Seymour Rosen

Keyword(s):

Epithelial Cells ◽

Proximal Tubule ◽

Renal Proximal Tubule ◽

Proliferation Capacity

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Faculty Opinions recommendation of Mitochondrial aquaporin-8 in renal proximal tubule cells: evidence for a role in the response to metabolic acidosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717948404.793453455 ◽

2012 ◽

Author(s):

Jeff Kraut

Keyword(s):

Metabolic Acidosis ◽

Proximal Tubule ◽

Renal Proximal Tubule ◽

Proximal Tubule Cells ◽

Tubule Cells ◽

Renal Proximal Tubule Cells

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Roles of Renal Proximal Tubule Transport in the Pathogenesis of Hypertension

Current Hypertension Reviews ◽

10.2174/15734021113099990009 ◽

2013 ◽

Vol 9 (2) ◽

pp. 148-155 ◽

Cited By ~ 11

Author(s):

Shoko Horita ◽

George Seki ◽

Hideomi Yamada ◽

Masashi Suzuki ◽

Kazuhiko Koike ◽

...

Keyword(s):

Proximal Tubule ◽

Renal Proximal Tubule

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Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis

Cells ◽

10.3390/cells10020414 ◽

2021 ◽

Vol 10 (2) ◽

pp. 414

Author(s):

Saja Baraghithy ◽

Yael Soae ◽

Dekel Assaf ◽

Liad Hinden ◽

Shiran Udi ◽

...

Keyword(s):

Bone Mass ◽

Proximal Tubule ◽

Bone Remodeling ◽

Kidney Function ◽

Bone Cells ◽

Critical Role ◽

Renal Proximal Tubule ◽

Proximal Tubule Cell ◽

Protective Effects ◽

Cannabinoid 1 Receptor

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB1R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB1R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB1R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

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Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability

Scientific Reports ◽

10.1038/s41598-021-89550-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vidya Chandrasekaran ◽

Giada Carta ◽

Daniel da Costa Pereira ◽

Rajinder Gupta ◽

Cormac Murphy ◽

...

Keyword(s):

Proximal Tubule ◽

Retinoic Acid Receptor ◽

Renal Proximal Tubule ◽

Whole Body ◽

Proper Function ◽

Genome Wide ◽

Glomerular Filtrate ◽

Proximal Tubular ◽

Induced Pluripotent

AbstractThe renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.

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