ReviewCalcium signaling

NAADP: A Universal Ca2+ Trigger

See allHide authors and affiliations

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

Figures

  • Fig. 1

    Structures of NAADP and NADP. The red circles highlight the only structural difference between them.

  • Fig. 2

    Schematic presentation of the NAADP–Ca2+ signaling pathway. Upon cell stimulation by an extracellular ligand, NAADP is formed and acts either on TRP-ML1 [inset taken from Kiselyov et al. (74) and modified] localized to acidic stores, or on type 1 RyR [inset taken from Zissimopoulos and Lai (75) and modified] localized to the ER. Transmembrane assignment of type 1 RyR is based on the 10 transmembrane model (76). Action on type 1 or 2 RyR may also proceed through an additional NAADP-binding protein. Initial trigger Ca2+ released through TRP-ML1 may be amplified through Ca2+-induced Ca2+ release through RyR (or IP3 receptors localized to ER; not shown). Ca2+ entry through the plasma membrane induced by NAADP may involve TRPM2 activation by adenosine diphosphoribose (TRPM2 also results in Na+ entry) or may occur secondary to store depletion and activation of CRACM1 (Orai1) by the capacitative mechanism.

  • Fig. 3

    NAD bound at the active site of CD38. The crystal structure of the extramembranous domain of human CD38 complexed with NAD was obtained by soaking NAD with crystals of an inactive mutant of CD38, E226Q 61.

Stay Connected to Science Signaling

Navigate This Article