ReviewCalcium signaling

NAADP: A Universal Ca2+ Trigger

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Sci. Signal.  04 Nov 2008:
Vol. 1, Issue 44, pp. re10
DOI: 10.1126/scisignal.144re10

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Intracellular signal transduction is fundamental to the ability of multicellular organisms to convert incoming signals into meaningful cellular responses. Calcium ions (Ca2+) released from intracellular stores transduce numerous physiological functions, from fertilization (at the beginning of life) to muscle contraction, induction of cell differentiation and proliferation, and finally apoptotic cell death. The free cytosolic Ca2+ concentration is much lower than that in the extracellular space or in intracellular stores, such as the endoplasmic reticulum (ER). Moreover, the free cytosolic Ca2+ concentration is tightly controlled through the activity of ion carrier proteins and adenosine 5′-triphosphate (ATP)–driven Ca2+ pumps, and through the open probability of Ca2+ channels. The latter is modulated by various mechanisms, including regulation by small signaling molecules generated in response to incoming extracellular signals, which are called second messengers. NAADP is the most recently identified and also the most potent messenger molecule known to mobilize Ca2+ stores in cells. Here, we summarize recent advances concerning NAADP, including the Ca2+ stores it targets, the receptor(s) with which it interacts, its Ca2+-signaling functions, and its metabolism, thereby unraveling a universal cellular signaling pathway.