PI3K intracellular signaling from cytoplasmic lipid droplets in transformed human mammary epithelial cells

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Cytoplasmic lipid droplets (CLDs) are associated with neutral lipids storage and lipid metabolism. Recent evidence suggests that CLDs might be involved in cell signaling. Here we unveil the function of CLDs as intracellular signaling platforms in breast epithelial cells. We establish that CLDs bear all the main components of the phosphatidylinositol-3 kinase (PI3K) pathway and that annexin II (Anx II) localizes to the CLDs in a phosphorylated form recruiting p85 to the CLDs, allowing the full activation of this pathway on CLDs. We also determine that reduction in CLDâ\#8364;™s formation by adipophilin and TIP47 knocking down correlates with a reduction in total cellular PI3K activity. Moreover, CLDs secreted by differentiated human mammary cells into the conditioned media retained components of the PI3K pathway. Similar results were obtained when purified mouse milk lipid globules (MLGs) were analyzed suggesting that CLDs secretion can be a mechanism to lower PI3K activity in differentiated breast epithelium during lactation. Our data suggest that CLDs, besides of its neutral lipid storage function, plays an important role in the intracellular signaling network may be comparable with the one assigned to endosomes.