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. 2023:278:3-34.
doi: 10.1007/164_2022_607.

NAADP-Mediated Ca2+ Signalling

Antony Galione  1 , Lianne C Davis  2 , Lora L Martucci  2 , Anthony J Morgan  2
Affiliations

NAADP-Mediated Ca2+ Signalling

Antony Galione et al. Handb Exp Pharmacol. 2023.

Abstract

The discovery of NAADP-evoked Ca2+ release in sea urchin eggs and then as a ubiquitous Ca2+ mobilizing messenger has introduced several novel paradigms to our understanding of Ca2+ signalling, not least in providing a link between cell stimulation and Ca2+ release from lysosomes and other acidic Ca2+ storage organelles. In addition, the hallmark concentration-response relationship of NAADP-mediated Ca2+ release, shaped by striking activation/desensitization mechanisms, influences its actions as an intracellular messenger. There has been recent progress in our understanding of the molecular mechanisms underlying NAADP-evoked Ca2+ release, such as the identification of the endo-lysosomal two-pore channel family of cation channels (TPCs) as their principal target and the identity of NAADP-binding proteins that complex with them. The NAADP/TPC signalling axis has gained recent prominence in pathophysiology for their roles in such disease processes as neurodegeneration, tumorigenesis and cellular viral entry.

Keywords: Acidic store; Ca2+; NAADP; Phosphatidylinositol 3,5 bisphosphate; Two-pore channel; lysosome.

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