TGF-β-induced Ca2+ influx involves the type III IP3 receptor and regulates actin cytoskeleton

Tracy A. McGowan, Muniswamy Madesh, Yanqing Zhu, Lewei Wang, Mark Russo, Leo Deelman, Rob Henning, Suresh Joseph, Gyorgy Hajnoczky, Kumar Sharma

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Ca2+ influx has been postulated to modulate the signaling pathway of transforming growth factor-β (TGF-β); however, the underlying mechanism and functional significance of TGF-β-induced stimulation of Ca2+ influx are unclear. We show here that TGF-β stimulates Ca2+ influx in mesangial cells without Ca2+ release. The influx of Ca2+ is prevented by pharmacological inhibitors of inositol 1,4,5-trisphosphate receptors (IP3R) as well as specific antibodies to type III IP3R (IP3RIII) but not to type I IP3R (IP3RI). TGF-β enhances plasma membrane localization of IP3RIII, whereas the sarcoplasmicendoplasmic reticulum Ca2+-ATPase (SERCA) preferentially translocates to the nucleus. Untreated mesangial cells exhibit actin filamentous protrusions on the cell surface, and treatment with TGF-β dramatically reduces this pattern. The alterations in the actin cytoskeleton by TGF-β are dependent on TGF-β-induced Ca2+ influx. These studies identify a novel pathway by which TGF-β regulates Ca2+ influx and induces cytoskeletal alterations.

Original languageEnglish (US)
Pages (from-to)F910-F920
JournalAmerican Journal of Physiology - Renal Physiology
Issue number5 51-5
StatePublished - 2002
Externally publishedYes


  • Filipodia
  • Inositol 1,4,5-trisphosphate
  • Mesangial cells
  • Signaling
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Urology
  • Physiology


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