TGF-beta-induced Ca(2+) influx involves the type III IP(3) receptor and regulates actin cytoskeleton

American Journal of Physiology. Renal Physiology
T A McGowanKumar Sharma

Abstract

Ca(2+) influx has been postulated to modulate the signaling pathway of transforming growth factor-beta (TGF-beta); however, the underlying mechanism and functional significance of TGF-beta-induced stimulation of Ca(2+) influx are unclear. We show here that TGF-beta stimulates Ca(2+) influx in mesangial cells without Ca(2+) release. The influx of Ca(2+) is prevented by pharmacological inhibitors of inositol 1,4,5-trisphosphate receptors (IP(3)R) as well as specific antibodies to type III IP(3)R (IP(3)RIII) but not to type I IP(3)R (IP(3)RI). TGF-beta enhances plasma membrane localization of IP(3)RIII, whereas the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) preferentially translocates to the nucleus. Untreated mesangial cells exhibit actin filamentous protrusions on the cell surface, and treatment with TGF-beta dramatically reduces this pattern. The alterations in the actin cytoskeleton by TGF-beta are dependent on TGF-beta-induced Ca(2+) influx. These studies identify a novel pathway by which TGF-beta regulates Ca(2+) influx and induces cytoskeletal alterations.

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Citations

Nov 13, 2003·Current Diabetes Reports·Gunter Wolf
Sep 15, 2005·American Journal of Physiology. Renal Physiology·Taishan HuKumar Sharma
Mar 17, 2007·American Journal of Respiratory and Critical Care Medicine·Jan HirschMichael A Matthay
Apr 24, 2008·The Journal of Clinical Investigation·Kumar SharmaBarry J Goldstein
Jul 26, 2008·American Journal of Physiology. Renal Physiology·Pál PacherGyörgy Hajnóczky
Sep 22, 2010·International Journal of Chronic Obstructive Pulmonary Disease·Kazuhito AsanoHiroaki Nakajima
Nov 18, 2016·American Journal of Respiratory Cell and Molecular Biology·Christie A OjiakuReynold A Panettieri
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Nov 9, 2006·American Journal of Physiology. Renal Physiology·Wanke ZhangBin-Xian Zhang
Jan 4, 2007·American Journal of Physiology. Renal Physiology·Satish P Ramachandra RaoKumar Sharma
Feb 9, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Samuel J GhilardiAllyson E Sgro
Mar 30, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Linlin GuA Brent Carter
Apr 9, 2013·The Journal of Biological Chemistry·Kurt A ZimmermanJoanne E Murphy-Ullrich
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Mar 31, 2011·The International Journal of Biochemistry & Cell Biology·Einsley JanowskiMartin Morad

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