Regulation and Function of TMEM16F in Renal Podocytes
The Ca2+-activated phospholipid scramblase and ion channel TMEM16F is expressed in podocytes of renal glomeruli. Podocytes are specialized cells that form interdigitating foot processes as an essential component of the glomerular filter. These cells, which participate in generation of the primary ur...
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doaj-84ed555cc6044a828db29fcc3558bf572020-11-25T00:17:14ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-06-01196179810.3390/ijms19061798ijms19061798Regulation and Function of TMEM16F in Renal PodocytesLaura K. Schenk0Jiraporn Ousingsawat1Boris V. Skryabin2Rainer Schreiber3Hermann Pavenstädt4Karl Kunzelmann5Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, 48149 Muenster, GermanyInstitut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, GermanyTransgenic Animal and Genetic Engineering Models (TRAM), Department of Medicine, Westfälischen, Wilhelms–Universität Münster, 48149 Münster, GermanyInstitut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, GermanyDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, 48149 Muenster, GermanyInstitut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, GermanyThe Ca2+-activated phospholipid scramblase and ion channel TMEM16F is expressed in podocytes of renal glomeruli. Podocytes are specialized cells that form interdigitating foot processes as an essential component of the glomerular filter. These cells, which participate in generation of the primary urine, are often affected during primary glomerular diseases, such as glomerulonephritis and secondary hypertensive or diabetic nephropathy, which always leads to proteinuria. Because the function of podocytes is known to be controlled by intracellular Ca2+ signaling, it is important to know about the role of Ca2+-activated TMEM16F in these cells. To that end, we generated an inducible TMEM16F knockdown in the podocyte cell line AB8, and produced a conditional mouse model with knockout of TMEM16F in podocytes and renal epithelial cells of the nephron. We found that knockdown of TMEM16F did not produce proteinuria or any obvious phenotypic changes. Knockdown of TMEM16F affected cell death of tubular epithelial cells but not of glomerular podocytes when analyzed in TUNEL assays. Surprisingly, and in contrast to other cell types, TMEM16F did not control intracellular Ca2+ signaling and was not responsible for Ca2+-activated whole cell currents in podocytes. TMEM16F levels in podocytes were enhanced after inhibition of the endolysosomal pathway and after treatment with angiotensin II. Renal knockout of TMEM16F did not compromise renal morphology and serum electrolytes. Taken together, in contrast to other cell types, such as platelets, bone cells, and immune cells, TMEM16F shows little effect on basal properties of podocytes and does not appear to be essential for renal function.http://www.mdpi.com/1422-0067/19/6/1798TMEM16Fanoctamin 6kidneyrenal ion channelschloride channel |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura K. Schenk Jiraporn Ousingsawat Boris V. Skryabin Rainer Schreiber Hermann Pavenstädt Karl Kunzelmann |
spellingShingle |
Laura K. Schenk Jiraporn Ousingsawat Boris V. Skryabin Rainer Schreiber Hermann Pavenstädt Karl Kunzelmann Regulation and Function of TMEM16F in Renal Podocytes International Journal of Molecular Sciences TMEM16F anoctamin 6 kidney renal ion channels chloride channel |
author_facet |
Laura K. Schenk Jiraporn Ousingsawat Boris V. Skryabin Rainer Schreiber Hermann Pavenstädt Karl Kunzelmann |
author_sort |
Laura K. Schenk |
title |
Regulation and Function of TMEM16F in Renal Podocytes |
title_short |
Regulation and Function of TMEM16F in Renal Podocytes |
title_full |
Regulation and Function of TMEM16F in Renal Podocytes |
title_fullStr |
Regulation and Function of TMEM16F in Renal Podocytes |
title_full_unstemmed |
Regulation and Function of TMEM16F in Renal Podocytes |
title_sort |
regulation and function of tmem16f in renal podocytes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-06-01 |
description |
The Ca2+-activated phospholipid scramblase and ion channel TMEM16F is expressed in podocytes of renal glomeruli. Podocytes are specialized cells that form interdigitating foot processes as an essential component of the glomerular filter. These cells, which participate in generation of the primary urine, are often affected during primary glomerular diseases, such as glomerulonephritis and secondary hypertensive or diabetic nephropathy, which always leads to proteinuria. Because the function of podocytes is known to be controlled by intracellular Ca2+ signaling, it is important to know about the role of Ca2+-activated TMEM16F in these cells. To that end, we generated an inducible TMEM16F knockdown in the podocyte cell line AB8, and produced a conditional mouse model with knockout of TMEM16F in podocytes and renal epithelial cells of the nephron. We found that knockdown of TMEM16F did not produce proteinuria or any obvious phenotypic changes. Knockdown of TMEM16F affected cell death of tubular epithelial cells but not of glomerular podocytes when analyzed in TUNEL assays. Surprisingly, and in contrast to other cell types, TMEM16F did not control intracellular Ca2+ signaling and was not responsible for Ca2+-activated whole cell currents in podocytes. TMEM16F levels in podocytes were enhanced after inhibition of the endolysosomal pathway and after treatment with angiotensin II. Renal knockout of TMEM16F did not compromise renal morphology and serum electrolytes. Taken together, in contrast to other cell types, such as platelets, bone cells, and immune cells, TMEM16F shows little effect on basal properties of podocytes and does not appear to be essential for renal function. |
topic |
TMEM16F anoctamin 6 kidney renal ion channels chloride channel |
url |
http://www.mdpi.com/1422-0067/19/6/1798 |
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