【多选题】How does the inositol phospholipid pathway trigger a rise in intracellular Ca 2+ ?
A.
Some GPCRs exert their effects through a G protein called G q , which activates the membrane-bound enzyme phospholipase C. Once activated, phospholipase C propagates the signal by cleaving a lipid molecule that is a component of the plasma membrane. The molecule is an inositol phospholipid that is present in small quantities in the cytosolic leaflet of the membrane lipid bilayer.
B.
Because of the involvement of this phospholipid, the signaling pathway that begins with the activation of phospholipase C is often referred to as the inositol phospholipid pathway. It operates in almost all eukaryotic cells and regulates a large number of different effector proteins.
C.
The cleavage of a membrane inositol phospholipid by phospholipase C generates two second messenger molecules: inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG). Both molecules play a crucial part in relaying the signal. IP 3 is a water-soluble sugar phosphate that is released into the cytosol; there it binds to and opens Ca 2+ channels that are embedded in the ER membrane. Ca 2+ stored inside the ER rushes out into the cytosol through these open channels, causing a sharp rise in the cytosolic concentration of free Ca 2+ , which is normally kept very low. This Ca 2+ in turn signals to other proteins.
D.
Diacylglycerol is a lipid that remains embedded in the plasma membrane after it is produced by phospholipase C; there, it helps recruit and activate a protein kinase, which translocates from the cytosol to the plasma membrane. This enzyme is called protein kinase C (PKC) because it also needs to bind Ca 2+ to become active. Once activated, PKC phosphorylates a set of intracellular proteins that varies depending on the cell type.