Positive regulation of inositol 1,4,5-trisphosphate-induced ca2+ release by mammalian target of rapamycin (mTOR) in RINm5F cells

✍ Scribed by Marc-Olivier Frégeau; Yannik Régimbald-Dumas; Prof. Gaétan Guillemette

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 361 KB
• Volume: 112
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.23006

✦ Synopsis

Abstract

The inositol 1,4,5‐trisphosphate receptor (IP~3~R), a ligand‐gated Ca^2+^ channel, is the main regulator of intracellular Ca^2+^ mobilization in non‐excitable cells. An emerging body of evidence suggests that specific regulatory control of the Ca^2+^ signaling pathway is modulated by the activation of additional signaling pathways. In the present study, we investigated the influence of the PI3‐kinase/mammalian target of rapamycin (mTOR) pathway on the activity of the IP~3~R/Ca^2+^ signaling pathway in RINm5F cells. We used a co‐immunoprecipitation approach to show that mTOR physically interacts with IP~3~R‐3 in an mTOR activity‐dependent manner. We also showed that IP~3~R is phosphorylated by mTOR in cellulo. All the conditions known to modulate mTOR activity (IGF‐1, wortmannin, rapamycin, PP242, and nutrient starvation) were shown to modify carbachol‐induced Ca^2+^ signaling in RINm5F cells. Lastly, we used an assay that directly measures the activity of IP~3~R, to show that mTOR increases the apparent affinity of IP~3~R. Given that mTOR controls cell proliferation and cell homeostasis, and that Ca^2+^ plays a key role in these two phenomena, it follows that mTOR facilitates IP~3~R‐mediated Ca^2+^ release when the nutritional status of cells requires it. J. Cell. Biochem. 112: 723–733, 2011. © 2011 Wiley‐Liss, Inc.