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Int. J. Mol. Sci. 2018, 19(6), 1798; https://doi.org/10.3390/ijms19061798

Regulation and Function of TMEM16F in Renal Podocytes

1
Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, 48149 Muenster, Germany
2
Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany
3
Transgenic Animal and Genetic Engineering Models (TRAM), Department of Medicine, Westfälischen, Wilhelms–Universität Münster, 48149 Münster, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 6 May 2018 / Revised: 12 June 2018 / Accepted: 14 June 2018 / Published: 18 June 2018
(This article belongs to the Special Issue Ion Transporters and Channels in Physiology and Pathophysiology)
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Abstract

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. View Full-Text
Keywords: TMEM16F; anoctamin 6; kidney; renal ion channels; chloride channel TMEM16F; anoctamin 6; kidney; renal ion channels; chloride channel
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Schenk, L.K.; Ousingsawat, J.; Skryabin, B.V.; Schreiber, R.; Pavenstädt, H.; Kunzelmann, K. Regulation and Function of TMEM16F in Renal Podocytes. Int. J. Mol. Sci. 2018, 19, 1798.

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