InsP3 Receptor Projects
The inositol 1,4,5-trisphosphate receptor (InsP3R) is activated when a ligand binds to its receptor (a hormone in this diagram). The binding of the hormone stimulates the trimeric G-protein to activate an enzyme, phospholipase C (PLC), which, in turn degrades the membrane lipid PIP2 into InsP3 and diacylglycerol (DAG). InsP3 binds to its receptor, opens the channel, and allows calcium to flow from the lumen of the endoplasmic reticulum to the cytoplasm. We are interested in how the InsP3R works, as a molecule, as a channel complex, and as a component of a complex signaling pathway.
Structure of the InsP3R
Regulation of the InsP3R
Regulation from the cytoplasmic side of the InsP3R
One of the many compounds which regulate the InsP3R from the cytoplasmic side is calcium. Free calcium exerts both stimulatory and inhibitory effects on the InsP3R type I. This regulation of the InsP3R by cytosolic calcium is highly concentration dependent where small elevations in cytosolic calcium concentrations (<300nM) increase channel open probability, however at higher free calcium concentrations, inhibition of InsP3R channel activity occurs. The cytoplasmic calcium-sensitivity of single InsP3R type II and type III channels is quite different from that described for the InsP3R type I where the calcium-dependency is sigmoidal with substantial channel activity occurring at calcium concentrations in the micromolar range. The combination of such isoform-specific properties with the sub-cellular distribution of the different isoforms may contribute to cellular mechanisms for coordinating calcium signals within the cell.