IP3

IP3, short for inositol 1,4,5-trisphosphate, is a water-soluble secondary messenger in many cellular signaling pathways. It is generated at the inner leaflet of the plasma membrane by the catalytic action of phospholipase C on the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) in response to activation of G protein-coupled receptors or receptor tyrosine kinases. Along with diacylglycerol (DAG), IP3 is produced as a result of PIP2 hydrolysis.

IP3 diffuses through the cytosol and binds to IP3 receptors (IP3R) on the membranes of the endoplasmic reticulum. This binding opens Ca2+ channels, releasing stored Ca2+ into the cytoplasm and triggering various Ca2+-dependent processes. The rise in cytosolic Ca2+ can activate enzymes, regulate ion channels, control exocytosis, and influence gene expression. IP3 signaling is often coupled with DAG signaling to activate protein kinase C and coordinate responses. Calcium signals can also trigger further IP3 production by feedback mechanisms.

IP3 receptors exist in several isoforms (IP3R1–IP3R3), encoded by ITPR1–ITPR3 genes, with distinct tissue distributions and regulatory properties. The intracellular Ca2+ release prompted by IP3 is modulated by multiple factors, including Ca2+-induced Ca2+ release and interactions with other signaling molecules.

Degradation of IP3 proceeds through dephosphorylation and phosphorylation to yield lower-order inositol phosphates and free inositol, which terminate the signal. IP3 plays a central role in diverse physiological processes such as neuronal signaling, muscle contraction, secretion, and development. Dysregulation of IP3 signaling has been implicated in various diseases, including neurodegenerative disorders and cancer.