Vhl deletion in renal epithelia causes HIF-1α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis

Renal ischemia causes redistribution of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) to the apical membrane of proximal tubules. We determined the time course of regeneration of Na(+)-K(+)-ATPase polarity and sought evidence of increased enzyme production during recovery as a means to restore polarity. Anesthetized rats underwent 45 min renal ischemia and reflow of 15 min, 2 h, 6 h, and 24 h. Immunofluorescent and electron microscopy showed loss of strict basolateral localization of Na(+)-K(+)-ATPase at 15 min reflow with repolarization by 24 h in sublethally injured cells. Both alpha 1- and beta-subunits were only in microsomal fractions at all reflow intervals. Immunodetectable levels of both subunits declined to 60-70% of control by 24 h reflow. Levels of mRNA for each subunit declined in parallel through 24 h to 55% of control. Overall transcription was profoundly depressed through 6 h but had recovered to near control by 24 h. Specific transcription of alpha 1- and beta-subunit mRNA was markedly decreased after ischemia and only partially recovered by 24 h. These results suggest that recycling of misplaced units rather than new Na(+)-K(+)-ATPase production is the means by which renal epithelia initially repolarize after ischemic injury.

Download Full-text

mLin-7 is localized to the basolateral surface of renal epithelia via its NH2 terminus

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.3.f464 ◽

2000 ◽

Vol 278 (3) ◽

pp. F464-F475 ◽

Cited By ~ 32

Author(s):

Samuel W. Straight ◽

David Karnak ◽

Jean-Paul Borg ◽

Emmanuel Kamberov ◽

Heidi Dare ◽

...

Keyword(s):

Amino Acids ◽

Growth Factor ◽

Receptor Tyrosine Kinase ◽

Growth Factor Receptor ◽

Kidney Cells ◽

Madin Darby Canine Kidney ◽

Renal Epithelia ◽

Renal Epithelial Cells ◽

Darby Canine Kidney ◽

Canine Kidney

In Caenorhabditis elegans, the basolateral localization of the Let-23 growth factor receptor tyrosine kinase requires the expression of three genes: lin-2, lin-7, and lin-10. Mammalian homologs of these three genes have been identified, and a complex of their protein products exists in mammalian neurons. In this paper, we examine the interaction of these mammalian proteins in renal epithelia. Coprecipitation experiments demonstrated that mLin-2/CASK binds to mLin-7, and immunofluorescent labeling showed that these proteins colocalized at the basolateral surface of Madin-Darby canine kidney cells and renal epithelia. Although labeling intensity varied markedly among different renal epithelial cells, those cells strongly expressing mLin-7 also showed intense mLin-2/CASK labeling. We have also demonstrated that mLin-2/CASK binding requires amino acids 12–32 of mLin-7 and have shown that this region of mLin-7 is also necessary for the targeting of mLin-7 to the basolateral surface. Furthermore, the overexpression of mLin-2/CASK mutants in Madin-Darby canine kidney cells caused endogenous mLin-7 to mislocalize. In summary, the NH2 terminus of mLin-7 is crucial for its basolateral localization, likely through its interaction with mLin-2/CASK.

Download Full-text

Sensory primary cilium is a responsive cAMP microdomain in renal epithelia

Scientific Reports ◽

10.1038/s41598-019-43002-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Rinzhin T. Sherpa ◽

Ashraf M. Mohieldin ◽

Rajasekharreddy Pala ◽

Dagmar Wachten ◽

Rennolds S. Ostrom ◽

...

Keyword(s):

Primary Cilium ◽

Renal Epithelia

Download Full-text

Platinum Complex Toxicity in Cultured Renal Epithelia

Cellular Physiology and Biochemistry ◽

10.1159/000080359 ◽

2004 ◽

Vol 14 (4-6) ◽

pp. 431-440 ◽

Cited By ~ 12

Author(s):

Thomas Ludwig ◽

Hans Oberleithner

Keyword(s):

Platinum Complex ◽

Renal Epithelia ◽

Cultured Renal Epithelia

Download Full-text

ADPKD: A Human Disease Altering Golgi Function and Basolateral Exocytosis in Renal Epithelia

Traffic ◽

10.1034/j.1600-0854.2000.010811.x ◽

2000 ◽

Vol 1 (8) ◽

pp. 675-686 ◽

Cited By ~ 30

Author(s):

Audra J. Charron ◽

Robert L. Bacallao ◽

Angela Wandinger-Ness

Keyword(s):

Human Disease ◽

Renal Epithelia

Download Full-text

Eicosanoids: Their Function in Renal Epithelia Ion Transport

Experimental Biology and Medicine ◽

10.3181/00379727-201-43503a ◽

1992 ◽

Vol 201 (3) ◽

pp. 229-243 ◽

Cited By ~ 16

Author(s):

L. W. Frazier ◽

T. Yorio

Keyword(s):

Ion Transport ◽

Renal Epithelia

Download Full-text

Native Polycystin 2 Functions as a Plasma Membrane Ca2+-Permeable Cation Channel in Renal Epithelia

Molecular and Cellular Biology ◽

10.1128/mcb.23.7.2600-2607.2003 ◽

2003 ◽

Vol 23 (7) ◽

pp. 2600-2607 ◽

Cited By ~ 131

Author(s):

Ying Luo ◽

Peter M. Vassilev ◽

Xiaogang Li ◽

Yoshifumi Kawanabe ◽

Jing Zhou

Keyword(s):

Plasma Membrane ◽

Mdck Cells ◽

Collecting Duct ◽

Cation Channel ◽

Surface Proteins ◽

Renal Epithelia ◽

Autosomal Dominant Polycystic Kidney ◽

Membrane Treatment ◽

Darby Canine Kidney

ABSTRACT Mutations in polycystin 2 (PC2), a Ca2+-permeable cation channel, cause autosomal dominant polycystic kidney disease. Whether PC2 functions in the endoplasmic reticulum (ER) or in the plasma membrane has been controversial. Here we generated and characterized a polyclonal antibody against PC2, determined the subcellular localization of both endogenous and transfected PC2 by immunohistochemistry and biotinylation of cell surface proteins, and assessed PC2 channel properties with electrophysiology. Endogenous PC2 was found in the plasma membrane and the primary cilium of mouse inner medullar collecting duct (IMCD) cells and Madin-Darby canine kidney (MDCK) cells, whereas heterologously expressed PC2 showed a predominant ER localization. Patch-clamping of IMCD cells expressing endogenous or heterologous PC2 confirmed the presence of the channel on the plasma membrane. Treatment with chaperone-like factors facilitated the translocation of the PC2 channel to the plasma membrane from intracellular pools. The unitary conductances, channel kinetics, and other characteristics of both endogenously and heterologously expressed PC2 were similar to those described in our previous study in Xenopus laevis oocytes. These results show that PC2 functions as a plasma membrane channel in renal epithelia and suggest that PC2 contributes to Ca2+ entry and transport of other cations in defined nephron segments in vivo.

Download Full-text