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 language | English (US) |
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Pages (from-to) | 715-726 |
Number of pages | 12 |
Journal | Cellular Physiology and Biochemistry |
Volume | 27 |
Issue number | 6 |
DOIs | |
State | Published - 2011 |
Keywords
- Calcium
- Cyst
- PI3K/Akt
- Polycystic Kidney Disease (ADPKD)
- Polycystin-1
- Polycystin-2
- STIM1
ASJC Scopus subject areas
- General Medicine