Question

Describe how ligand binding to a receptor leads to the production of IP₃ and DAG and the release of Ca^2+.

Short answer

The binding of a ligand to its corresponding Gq protein-coupled receptor initiates the phosphoinositide pathway, which activates phospholipase C (PLC) to hydrolyze the membrane lipid PIP₂ to the second messengers IP₃ and DAG. IP₃ causes the release of Ca²⁺ from the endoplasmic reticulum, DAG activates protein kinase C (PKC), and Ca²⁺ activates both PKC and Ca²⁺-calmodulin-dependent protein kinase (CaMK).

Step-by-step solution

IP3 stimulates the release of Ca2+

Activated phospholipase C catalyzes the hydrolysis ofPIP₂toIP₃and DAG.The water-soluble IP₃ stimulates the release of Ca²⁺ sequestered in the endoplasmic reticulum, activating numerous cellular processes through calmodulin (CaM) intermediacy.

Activation of phospholipase C

Ligand binding to a cell-surface receptor R activates phospholipase C (PLC) through the heterotrimeric G protein Gq.

DAG activates PKC

The nonpolar DAG remains associated with the membrane, where it activates protein kinase C (PKC) to phosphorylate, thereby modulating several cellular proteins' activities. PKC activation also requires the presence of the membrane lipid phosphatidylserine (PS) and Ca²⁺.