Polycystin-1, 2, and STIM1 interact with IP 3 R to Modulate ER Ca 2+ release through the PI3K/Akt pathway

Research output: Contribution to journalArticlepeer-review

Abstract

Dysregulation of Ca 2+ signaling and homeostasis has been linked to the development of ADPKD through aberrant functioning of the polycystins. In this study, we investigated the role of the polycystins in modulating Ca 2+ signaling. Expression of full-length PC1 in MDCK cells inhibited intracellular Ca 2+ release in response to ATP when compared to control cells. This phenotype correlated with reduced interaction of endogenous PC2 and IP 3 R in PC1-containing cells. We also found that endogenous STIM1 also interacted with the IP 3 R, and this interaction was enhanced by PC1 expression. Increased interaction between STIM1 and IP 3 R inhibited Ca 2+ release. PC1 regulates intracellular Ca 2+ release and the interaction of PC2-IP 3 R-STIM1 through the PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt pathway in PC1 containing cells restored intracellular Ca 2+ release, increased the interaction between PC2 and IP 3 R and disrupted the STIM1-IP 3 R complex. Conversely, activation of the PI3K/Akt signaling pathway by HGF in control MDCK cells gave the reverse effects. It reduced the release of Ca 2+ to levels comparable to the PC1 cells, inhibited the association PC2 and IP 3 R, and increased the interaction between STIM and IP 3 R. Overall, our studies provide a potential mechanism for the modulation of intracellular Ca 2+ signaling by the polycystins.

Original languageEnglish (US)
Pages (from-to)715-726
Number of pages12
JournalCellular Physiology and Biochemistry
Volume27
Issue number6
DOIs
StatePublished - 2011

Keywords

  • Calcium
  • Cyst
  • PI3K/Akt
  • Polycystic Kidney Disease (ADPKD)
  • Polycystin-1
  • Polycystin-2
  • STIM1

ASJC Scopus subject areas

  • Physiology

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