Calcium signaling pathway

Calcium (Ca2+) serves as a universal second messenger in all eukaryotes. The importance of Ca2+ signaling pathway for the implementation of the information provided by Ca2+ has been increasingly appreciated, and several distinct families of Ca2+ sensing proteins have been identified and characterized. As it shows in the following picture, there are two principal source of Ca2+ for signaling. One principal source of signal Ca2+ is that enters the cell from the outside. Entry of Ca2+ is driven by the emergence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. Besides, there are also many other Ca2+-entry channels, including the receptor-operated channels (ROCs), second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). Another principal source of Ca2+ signaling is internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR). And inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+ in ER/SR. The primary activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is critical to the mechanism of Ca2+ signaling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways with different isoforms of phospholipase C, regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs.

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