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NAADP-Mediated Ca2+ Signalling.

Antony Galione1, Lianne C Davis2, Lora L Martucci2

  • 1Department of Pharmacology, University of Oxford, Oxford, UK. antony.galione@pharm.ox.ac.uk.

Handbook of Experimental Pharmacology
|July 25, 2022
PubMed
Summary
This summary is machine-generated.

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a key messenger for calcium release from acidic stores like lysosomes. Its signaling pathway involves two-pore channels (TPCs) and is implicated in diseases such as neurodegeneration and cancer.

Keywords:
Acidic storeCa2+NAADPPhosphatidylinositol 3,5 bisphosphateTwo-pore channellysosome

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Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Calcium Homeostasis

Background:

  • Calcium (Ca2+) signaling is fundamental to cellular processes.
  • Nicotinic acid adenine dinucleotide phosphate (NAADP) acts as a ubiquitous Ca2+ mobilizing messenger.
  • NAADP links cell stimulation to Ca2+ release from acidic organelles, including lysosomes.

Purpose of the Study:

  • To elucidate the novel paradigms introduced by NAADP-evoked Ca2+ release.
  • To understand the concentration-response relationship and activation/desensitization mechanisms of NAADP.
  • To identify the molecular targets and binding proteins involved in NAADP signaling.

Main Methods:

  • Investigated NAADP-evoked Ca2+ release mechanisms.
  • Identified the role of endo-lysosomal two-pore channel family (TPCs) as principal targets.
  • Characterized NAADP-binding proteins that complex with TPCs.

Main Results:

  • Established NAADP as a critical regulator of Ca2+ release from acidic stores.
  • Identified TPCs as the primary molecular targets for NAADP-mediated Ca2+ mobilization.
  • Uncovered the involvement of specific NAADP-binding proteins in the signaling complex.

Conclusions:

  • The NAADP/TPC signaling axis represents a novel paradigm in Ca2+ signaling.
  • This pathway is crucial for linking cellular stimuli to Ca2+ release from lysosomes.
  • The NAADP/TPC axis is increasingly recognized for its role in diseases like neurodegeneration, tumorigenesis, and viral entry.