scholarly journals NAADP: From Discovery to Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Timothy F. Walseth ◽  
Andreas H. Guse
Keyword(s):  
Nicotinic Acid ◽  
Binding Protein ◽  
Cell Types ◽  
Fundamental Question ◽  
Current Evidence ◽  
High Affinity ◽  
Naturally Occurring ◽  
Release Mechanisms

Nicotinic acid adenine dinucleotide 2’-phosphate (NAADP) is a naturally occurring nucleotide that has been shown to be involved in the release of Ca2+ from intracellular stores in a wide variety of cell types, tissues and organisms. Current evidence suggests that NAADP may function as a trigger to initiate a Ca2+ signal that is then amplified by other Ca2+ release mechanisms. A fundamental question that remains unanswered is the identity of the NAADP receptor. Our recent studies have identified HN1L/JPT2 as a high affinity NAADP binding protein that is essential for the modulation of Ca2+ channels.

scholarly journals Unique kinetics of nicotinic acid–adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand

2000 ◽  
Vol 352 (3) ◽  
pp. 725-729 ◽  
Author(s):  
Sandip PATEL ◽  
Grant C. CHURCHILL ◽  
Antony GALIONE
Keyword(s):  
Nicotinic Acid ◽  
Sea Urchin ◽  
Binding Sites ◽  
Cell Types ◽  
Unique Property ◽  
Single Class ◽  
High Affinity ◽  
Sea Urchin Egg ◽  
Low Concentrations ◽  
Kinetics Of

Nicotinic acidŐadenine dinucleotide phosphate (NAADP) is a novel and potent Ca2+-mobilizing agent in sea urchin eggs and other cell types. Little is known, however, concerning the properties of the putative intracellular NAADP receptor. In the present study we have characterized NAADP binding sites in sea urchin egg homogenates. [32P]NAADP bound to a single class of high-affinity sites that were reversibly inhibited by NaCl but insensitive to pH and Ca2+. Binding of [32P]NAADP was lost in preparations that did not mobilize Ca2+ in response to NAADP, indicating that [32P]NAADP probably binds to a receptor mediating Ca2+ mobilization. Addition of excess unlabelled NAADP, at various times after initiation of [32P]NAADP binding, did not result in displacement of bound [32P]NAADP. These data show that NAADP becomes irreversibly bound to its receptor immediately upon association. Accordingly, incubation of homogenates with low concentrations of NAADP resulted in maximal labelling of NAADP binding sites. This unique property renders NAADP receptors exquisitely sensitive to their ligand, thereby allowing detection of minute changes in NAADP levels.

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