Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

scholarly journals Role of adenosine on glucagon-induced cAMP in a human cortical collecting duct cell line

1995 ◽  
Vol 47 (5) ◽  
pp. 1310-1318 ◽  
Author(s):  
Dominique Prié ◽  
Gérard Friedlander ◽  
Christiane Coureau ◽  
Alain Vandewalle ◽  
Roland Cassingéna ◽  
...  
Keyword(s):  
Cell Line ◽  
Collecting Duct ◽  
Duct Cell ◽  
Cortical Collecting Duct

Potassium Transport in the Mammalian Collecting Duct

2001 ◽  
Vol 81 (1) ◽  
pp. 85-116 ◽  
Author(s):  
Shigeaki Muto
Keyword(s):  
Driving Forces ◽  
Collecting Duct ◽  
Dominant Role ◽  
Duct Cell ◽  
Cell Types ◽  
Cortical Collecting Duct ◽  
Membrane Conductances ◽  
Collecting Duct Cells

The mammalian collecting duct plays a dominant role in regulating K+ excretion by the nephron. The collecting duct exhibits axial and intrasegmental cell heterogeneity and is composed of at least two cell types: collecting duct cells (principal cells) and intercalated cells. Under normal circumstances, the collecting duct cell in the cortical collecting duct secretes K+, whereas under K+ depletion, the intercalated cell reabsorbs K+. Assessment of the electrochemical driving forces and of membrane conductances for transcellular and paracellular electrolyte movement, the characterization of several ATPases, patch-clamp investigation, and cloning of the K+ channel have provided important insights into the role of pumps and channels in those tubule cells that regulate K+ secretion and reabsorption. This review summarizes K+ transport properties in the mammalian collecting duct. Special emphasis is given to the mechanisms of how K+ transport is regulated in the collecting duct.

Asymmetry in the Osmotic Response of a Rat Cortical Collecting Duct Cell Line: Role of Aquaporin-2

2005 ◽  
Vol 207 (3) ◽  
pp. 143-150 ◽  
Author(s):  
O. Chara ◽  
P. Ford ◽  
V. Rivarola ◽  
M. Parisi ◽  
C. Capurro
Keyword(s):  
Cell Line ◽  
Collecting Duct ◽  
Duct Cell ◽  
Cortical Collecting Duct ◽  
Aquaporin 2 ◽  
Osmotic Response

scholarly journals Intraflagellar transport-A deficiency attenuates ADPKD in a renal tubular- and maturation-dependent manner

2020 ◽  
Author(s):  
Wei Wang ◽  
Luciane M. Silva ◽  
Henry H. Wang ◽  
Matthew A. Kavanaugh ◽  
Tana S. Pottorf ◽  
...  
Keyword(s):  
Mouse Models ◽  
Primary Cilia ◽  
Protein Complexes ◽  
Collecting Duct ◽  
Intraflagellar Transport ◽  
Renal Tubules ◽  
Dependent Manner ◽  
Cortical Collecting Duct ◽  
Knock Out

AbstractPrimary cilia are sensory organelles that are built and maintained by intraflagellar transport (IFT) multi-protein complexes. Deletion of certain ciliary genes in Autosomal Dominant Polycystic Kidney Disease (ADPKD) mouse models markedly attenuates PKD severity, indicating that a component of cilia dysfunction may have potential therapeutic value. To broaden the role of ciliary dysfunction, here we investigate the role of global deletion of Ift-A gene, Thm1, in juvenile and adult ADPKD mouse models. In cyst-lining cells of both juvenile and adult ADPKD models, cortical collecting duct cilia lengths and cytoplasmic and nuclear levels of the nutrient sensor, O-linked β-Nacetylglucosamine (O-GlcNAc) were increased. Relative to juvenile Pkd2 conditional knock-out mice, deletion of Thm1 together with Pkd2 both increased and reduced cystogenesis in a tubule-specific manner without altering kidney function, inflammation, cilia lengths, and ERK, STAT3 and OGlcNAc signaling. In contrast, Thm1 deletion in adult ADPKD mouse models markedly attenuated almost all features of PKD, including renal cystogenesis, inflammation, cilia lengths, and ERK, STAT3 and O-GlcNAc signaling. These data suggest that differential factors in the microenvironments between renal tubules and between developing and mature kidneys influence cilia and ADPKD pathobiology. Further, since O-GlcNAcylation directly regulates ciliary homeostasis and the balance between glycolysis and oxidative phosphorylation, we propose that increased O-GlcNAcylation may promote certain key ADPKD pathological processes.

scholarly journals Cilia movement regulates expression of the Raf-1 kinase inhibitor protein

2011 ◽  
Vol 300 (5) ◽  
pp. F1163-F1170 ◽  
Author(s):  
Kelli M. Sas ◽  
Michael G. Janech ◽  
Elizabeth Favre ◽  
John M. Arthur ◽  
P. Darwin Bell
Keyword(s):  
Primary Cilia ◽  
Kinase Inhibitor ◽  
Mapk Pathway ◽  
Collecting Duct ◽  
Duct Cell ◽  
Inhibitor Protein ◽  
Ciliary Movement ◽  
Renal Epithelial Cell ◽  
Adult Mice

Renal epithelial cell primary cilia act as mechanosensors in response to changes in luminal fluid flow. To determine the role of cilia bending in the mechanosensory function of cilia, we performed proteomic analysis of collecting duct cell lines with or without cilia that were kept stationary or rotated to stimulate cilia bending. Expression of the Raf-1 kinase inhibitor protein (RKIP), an inhibitor of the MAPK pathway, was significantly elevated in rotated cilia (+) cells. This was compared with RKIP levels in cilia (−) cells that were stationary or rotated as well as in cilia (+) cells that were stationary. This result was confirmed in cilia knockout adult mice that had lower renal RKIP levels compared with adult mice with cilia. Downstream of RKIP, expression of phosphorylated ERK was decreased only in cells that had cilia and were subjected to constant cilia bending. Furthermore, elevated RKIP levels were associated with reduced cell proliferation. Blockade of PKC abrogated ciliary bending-induced increases in RKIP. In summary, we found that ciliary movement may help control the expression of the Raf-1 kinase inhibitor protein and thus maintain cell differentiation. In terms of polycystic kidney disease, loss of cilia and therefore sensitivity to flow may lead to reduced RKIP levels, activation of the MAPK pathway, and contribute to the formation of cysts.

Differential Role of Na+/H+ Exchange Isoforms NHE-1 and NHE-2 in a Rat Cortical Collecting Duct Cell Line

2002 ◽  
Vol 190 (2) ◽  
pp. 117-125 ◽  
Author(s):  
P. Ford ◽  
V. Rivarola ◽  
A. Kierbel ◽  
O. Chara ◽  
M. Blot-Chabaud ◽  
...  
Keyword(s):  
Cell Line ◽  
Collecting Duct ◽  
Duct Cell ◽  
Cortical Collecting Duct

scholarly journals Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease

2008 ◽  
Vol 183 (3) ◽  
pp. 377-384 ◽  
Author(s):  
Julie A. Jonassen ◽  
Jovenal San Agustin ◽  
John A. Follit ◽  
Gregory J. Pazour
Keyword(s):  
Kidney Disease ◽  
Primary Cilia ◽  
Collecting Duct ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Duct Cells ◽  
Cell Proliferation And Differentiation ◽  
Cilia Formation ◽  
Collecting Duct Cells

Primary cilia project from the surface of most vertebrate cells and are thought to be sensory organelles. Defects in primary cilia lead to cystic kidney disease, although the ciliary mechanisms that promote and maintain normal renal function remain incompletely understood. In this work, we generated a floxed allele of the ciliary assembly gene Ift20. Deleting this gene specifically in kidney collecting duct cells prevents cilia formation and promotes rapid postnatal cystic expansion of the kidney. Dividing collecting duct cells in early stages of cyst formation fail to properly orient their mitotic spindles along the tubule, whereas nondividing cells improperly position their centrosomes. At later stages, cells lacking cilia have increased canonical Wnt signaling and increased rates of proliferation. Thus, IFT20 functions to couple extracellular events to cell proliferation and differentiation.

scholarly journals Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 348-352
Author(s):  
Emilija Golubovic
Keyword(s):  
Kidney Disease ◽  
Mammalian Cells ◽  
Autosomal Recessive ◽  
Primary Cilia ◽  
Calcium Influx ◽  
Control Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Cystic Disease ◽  
Renal Cystic Disease

Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis-medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

scholarly journals Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium

2021 ◽  
Author(s):  
Stephanie Probst ◽  
Johannes Fels ◽  
Bettina Scharner ◽  
Natascha A. Wolff ◽  
Eleni Roussa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Fate ◽  
Catalase Activity ◽  
Metal Ion ◽  
Iron Homeostasis ◽  
Collecting Duct ◽  
Duct Cell ◽  
Plasmid Transfection

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis. Hepcidin is also expressed by the kidney, but exclusively in distal nephron segments. Several studies suggest hepcidin protects against kidney damage involving Fe2+ overload. The nephrotoxic non-essential metal ion Cd2+ can displace Fe2+ from cellular biomolecules, causing oxidative stress and cell death. The role of hepcidin in Fe2+ and Cd2+ toxicity was assessed in mouse renal cortical [mCCD(cl.1)] and inner medullary [mIMCD3] collecting duct cell lines. Cells were exposed to equipotent Cd2+ (0.5–5 μmol/l) and/or Fe2+ (50–100 μmol/l) for 4–24 h. Hepcidin (Hamp1) was transiently silenced by RNAi or overexpressed by plasmid transfection. Hepcidin or catalase expression were evaluated by RT-PCR, qPCR, immunoblotting or immunofluorescence microscopy, and cell fate by MTT, apoptosis and necrosis assays. Reactive oxygen species (ROS) were detected using CellROX™ Green and catalase activity by fluorometry. Hepcidin upregulation protected against Fe2+-induced mIMCD3 cell death by increasing catalase activity and reducing ROS, but exacerbated Cd2+-induced catalase dysfunction, increasing ROS and cell death. Opposite effects were observed with Hamp1 siRNA. Similar to Hamp1 silencing, increased intracellular Fe2+ prevented Cd2+ damage, ROS formation and catalase disruption whereas chelation of intracellular Fe2+ with desferrioxamine augmented Cd2+ damage, corresponding to hepcidin upregulation. Comparable effects were observed in mCCD(cl.1) cells, indicating equivalent functions of renal hepcidin in different collecting duct segments. In conclusion, hepcidin likely binds Fe2+, but not Cd2+. Because Fe2+ and Cd2+ compete for functional binding sites in proteins, hepcidin affects their free metal ion pools and differentially impacts downstream processes and cell fate.

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