Phosphoinositide is a family of phospholipids fundamental to almost all cellular functions. Abnormal phosphoinositide metabolism is linked to numerous diseases including cancer, neuropathy, and myopathy. The level of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2), a phosphoinositide enriched at the plasma membrane (PM), regulates membrane trafficking, ion transport, and cytoskeleton dynamics. During receptor-induced calcium signaling, PI(4,5)P2 is hydrolyzed by phospholipase C (PLC) to produce inositol triphosphate (IP3) that releases calcium from the endoplasmic reticulum (ER) to initiate calcium signaling. To sustain PI(4,5)P2-dependent functions during receptor-induced calcium signaling, PI synthesized in the ER is transferred to the PM to be converted to PI(4,5)P2, whereas phosphatidic acid (PA), a metabolic product of PI(4,5)P2, is transferred to the ER for PI synthesis. This homeostatic process maintaining the level of PI(4,5)P2 at the PM during receptor stimulation is known as the PI cycle.
Our research has revealed that
- Nir2 is a PI transfer protein that dynamically localizes to ER-PM junctions during calcium signaling