Integration of nicotinic acid adenine dinucleotide phosphate (NAADP)‐dependent calcium signalling

Abstract

Nicotinic acid adenine dinucleotide phosphate (NAADP) is currently the most potent endogenous Ca mobilizing second messenger. Upon specific extracellular stimulation, rapid production of NAADP has been observed in different cell types from sea urchin eggs to mammalian cells. More than 20 years after the discovery of NAADP, there is still controversy surrounding its metabolism and target receptors/ion channels and organelles. This article briefly reviews recent developments in the NAADP field. Besides the metabolism of NAADP, this review focuses on assumed organelles and putative targets, e.g. ion channels, with special emphasis on ryanodine receptor type 1 (RyR1) and two-pore channels (TPCs). The role of NAADP as a Ca trigger is also discussed and the importance of NAADP in the formation of initial Ca microdomains is highlighted.

Endothelial Ca2+ Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel

“…NAADP and TPC1-2 regulate a growing number of functions, including autophagy, nutrient sensing, membrane trafficking, exocytosis, fertilization and embryogenesis, proliferation and synaptic transmission [105,106,107,108]. NAADP synthesis has been attributed to the multifunctional enzyme CD38, although NAADP levels are increased, rather than decreased, by genetic suppression of CD38 in several murine tissues [109]. However, CD38 is expressed in endothelial cells [110] and NAADP is synthesized in response to endothelial autacoids, such as histamine [111].…”

Endolysosomal Ca2+ Signalling and Cancer Hallmarks: Two-Pore Channels on the Move, TRPML1 Lags Behind!

“…The gating mechanisms of TPCs and their permeability properties have engendered a durable controversy that is yet to be fully resolved [103,123,124,125,126]. TPC1-2 were first identified as the long-sought target for the intracellular second messenger, NAADP, which is synthesized in response to multiple extracellular stimuli by the ADP-ribosyl cyclase, CD38 [127]. A wealth of robust evidences clearly converged on this evidence.…”

Gordon Research Conference on Ca2+ Signalling 2017 Editorial

“…There is considerable debate as to which organelles and ion channels are targeted by NAADP. The review by Guse and Diercks () discusses how NAADP‐binding proteins that act as NAADP receptors might couple with different ion channels located on different Ca 2+ stores. This unifying hypothesis can help explain some of the conflicting results in the field and would allow for a highly versatile and flexible use of NAADP as an intracellular Ca 2+ releasing agent.…”