NAADP signaling revisited

Area of Science:

• Biochemistry
• Cell Biology
• Physiology

Background:

• Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent endogenous Ca²⁺-mobilizing second messenger.
• Its Ca²⁺-releasing activity is observed across various cell types and in response to diverse stimuli.
• However, several aspects of NAADP signaling remain incompletely understood.

Purpose of the Study:

• To review and clarify controversial aspects of NAADP signaling.
• To discuss NAADP's role as a second messenger, including its endogenous concentrations, receptor-mediated regulation, metabolism, and potential targets.
• To examine NAADP's function as a Ca²⁺ trigger, focusing on the transition from local to global Ca²⁺ signals.

Main Methods:

• Literature review and critical analysis of existing research on NAADP signaling.
• Synthesis of data concerning NAADP's endogenous levels, metabolic pathways, and interactions with cellular organelles and ion channels.
• Discussion of experimental evidence supporting NAADP's role in initiating and shaping Ca²⁺ signals.

Main Results:

• NAADP's precise endogenous concentrations and their regulation by receptors are subjects of ongoing investigation.
• Multiple organelle and ion channel targets are proposed for NAADP, contributing to its complex signaling network.
• NAADP initiates localized Ca²⁺ signals that can propagate to evoke global cellular Ca²⁺ responses.

Conclusions:

• NAADP plays a critical, albeit complex, role in cellular calcium homeostasis and signaling.
• Further research is needed to fully elucidate NAADP's precise mechanisms of action, its regulatory pathways, and its specific molecular targets.
• Understanding NAADP signaling is crucial for deciphering cellular responses to various stimuli and for potential therapeutic interventions.