NAADP: A Universal Ca²⁺ Trigger

Andreas H. Guse^1* and Hon Cheung Lee²

¹ The Calcium Signaling Group, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20146 Hamburg, Germany.
² Department of Physiology, The Hong Kong University, 4/F Lab Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong.

Gloss: 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.

* Corresponding author. E-mail, guse{at}uke.uni-hamburg.de

The editors suggest the following Related Resources on Science sites:

In Science Signaling

RESEARCH
Ion Channels
TRPM2 Functions as a Lysosomal Ca²⁺-Release Channel in β Cells

Ingo Lange, Shinichiro Yamamoto, Santiago Partida-Sanchez, Yasuo Mori, Andrea Fleig, and Reinhold Penner (19 May 2009)
Sci. Signal. 2 (71), ra23. [DOI: 10.1126/scisignal.2000278]
 |  Editor's Summary »  |  Abstract »  |  Full Text »  |  PDF »  |  Supplementary Materials »

MEETING REPORTS
Cell Biology
Emerging Roles of NAD⁺ and Its Metabolites in Cell Signaling

Friedrich Koch-Nolte, Friedrich Haag, Andreas H. Guse, Frances Lund, and Mathias Ziegler (10 February 2009)
Sci. Signal. 2 (57), mr1. [DOI: 10.1126/scisignal.257mr1]
 |  Abstract »  |  Full Text »  |  PDF »

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES: