TPC: the NAADP discovery channel?

2015 ◽  
Vol 43 (3) ◽  
pp. 384-389 ◽  
Author(s):  
Anthony J. Morgan ◽  
Lianne C. Davis ◽  
Margarida Ruas ◽  
Antony Galione
Keyword(s):  
Nicotinic Acid ◽  
Recent Work ◽  
Second Messenger ◽  
Release Channel

The Ca2+-mobilizing second messenger, NAADP (nicotinic acid adenine dinucleotide phosphate), has been with us for nearly 20 years and yet we still cannot fully agree on the identity of its target Ca2+-release channel. In spite of some recent robust challenges to the idea that two-pore channels (TPCs) represent the elusive “NAADP receptor”, evidence continues to accumulate that TPCs are important for NAADP-mediated responses. This article will briefly outline the background and review more recent work pertaining to the TPC story.

scholarly journals Nicotinic acid–adenine dinucleotide phosphate activates the skeletal muscle ryanodine receptor

2002 ◽  
Vol 367 (2) ◽  
pp. 423-431 ◽  
Author(s):  
Martin HOHENEGGER ◽  
Josef SUKO ◽  
Regina GSCHEIDLINGER ◽  
Helmut DROBNY ◽  
Andreas ZIDAR
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Nicotinic Acid ◽  
Ryanodine Receptor ◽  
Spatial Information ◽  
Single Channel ◽  
Reversal Potential ◽  
Open Probability ◽  
Release Channel

Calcium is a universal second messenger. The temporal and spatial information that is encoded in Ca2+-transients drives processes as diverse as neurotransmitter secretion, axonal outgrowth, immune responses and muscle contraction. Ca2+-release from intracellular Ca2+ stores can be triggered by diffusible second messengers like InsP3, cyclic ADP-ribose or nicotinic acid—adenine dinucleotide phosphate (NAADP). A target has not yet been identified for the latter messenger. In the present study we show that nanomolar concentrations of NAADP trigger Ca2+-release from skeletal muscle sarcoplasmic reticulum. This was due to a direct action on the Ca2+-release channel/ryanodine receptor type-1, since in single channel recordings, NAADP increased the open probability of the purified channel protein. The effects of NAADP on Ca2+-release and open probability of the ryanodine receptor occurred over a similar concentration range (EC5030nM) and were specific because (i) they were blocked by Ruthenium Red and ryanodine, (ii) the precursor of NAADP, NADP, was ineffective at equimolar concentrations, (iii) NAADP did not affect the conductance and reversal potential of the ryanodine receptor. Finally, we also detected an ADP-ribosyl cyclase activity in the sarcoplasmic reticulum fraction of skeletal muscle. This enzyme was not only capable of synthesizing cyclic GDP-ribose but also NAADP, with an activity of 0.25nmol/mg/min. Thus, we conclude that NAADP is generated in the vicinity of type 1 ryanodine receptor and leads to activation of this ion channel.

N-terminal tagging of two-pore channels interferes with NAADP action

2013 ◽  
Vol 453 (1) ◽  
pp. e1-e2 ◽  
Author(s):  
Andreas H. Guse
Keyword(s):  
Nicotinic Acid ◽  
Protein Targeting ◽  
Second Messenger ◽  
Terminal Region ◽  
Receptor Protein ◽  
Pore Channel ◽  
Biochemical Journal ◽  
N Terminus

NAADP (nicotinic acid–adenine dinucleotide phosphate) is the most potent Ca2+-releasing second messenger known to date. Since its discovery in 1995 identifying the NAADP receptor protein/Ca2+ channel has been a major persuit of the Ca2+ signalling community. In their paper ‘The N-terminal region of two-pore channel 1 regulates trafficking and activation by NAADP’ published in this issue of the Biochemical Journal Patel and colleagues describe that the N-terminus of one of the NAADP receptor protein/Ca2+ channel candidates, TPC1 (two-pore channel 1), is crucial for protein targeting and for sensitivity to NAADP.

Can Learning and Memory Be Understood?

Physiology ◽  
1986 ◽  
Vol 1 (6) ◽  
pp. 182-185
Author(s):  
JH Byrne
Keyword(s):  
Associative Learning ◽  
Learning And Memory ◽  
Recent Work ◽  
Neural Circuits ◽  
Second Messenger ◽  
Nerve Cells ◽  
Learned Behavior ◽  
Second Messenger Systems ◽  
Mechanistic Understanding ◽  
The Mind

Progress in unraveling the mysteries of the mind has been slow, but recent work indicates that a complete mechanistic understanding of at least simple forms of learning will soon be in hand. For example, it is becoming evident that associative learning is due to changes in existing neural circuits and that the acquisition of a learned behavior is due to the activation of second messenger systems in nerve cells.

scholarly journals Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Is a Second Messenger in Muscarinic Receptor-induced Contraction of Guinea Pig Trachea

2013 ◽  
Vol 288 (16) ◽  
pp. 10986-10993 ◽  
Author(s):  
Parvinder K. Aley ◽  
Nisha Singh ◽  
G. Cristina Brailoiu ◽  
Eugen Brailoiu ◽  
Grant C. Churchill
Keyword(s):  
Guinea Pig ◽  
Nicotinic Acid ◽  
Muscarinic Receptor ◽  
Second Messenger

scholarly journals Calcium Signaling in Cholangiocytes: Methods, Mechanisms, and Effects

2018 ◽  
Vol 19 (12) ◽  
pp. 3913 ◽  
Author(s):  
Michele Rodrigues ◽  
Dawidson Gomes ◽  
Michael Nathanson
Keyword(s):  
Calcium Signaling ◽  
Second Messenger ◽  
Experimental Models ◽  
Cell Type ◽  
Release Channel ◽  
Cellular Processes ◽  
Inositol 1,4,5 Trisphosphate ◽  
Regulation Of Secretion ◽  
Trisphosphate Receptor

Calcium (Ca2+) is a versatile second messenger that regulates a number of cellular processes in virtually every type of cell. The inositol 1,4,5-trisphosphate receptor (ITPR) is the only intracellular Ca2+ release channel in cholangiocytes, and is therefore responsible for Ca2+-mediated processes in these cells. This review will discuss the machinery responsible for Ca2+ signals in these cells, as well as experimental models used to investigate cholangiocyte Ca2+ signaling. We will also discuss the role of Ca2+ in the normal and abnormal regulation of secretion and apoptosis in cholangiocytes, two of the best characterized processes mediated by Ca2+ in this cell type.

scholarly journals Calcium signalling: NAADP comes out of the shadows

2003 ◽  
Vol 373 (1) ◽  
pp. e3-e4 ◽  
Author(s):  
Guy A. RUTTER
Keyword(s):  
Nicotinic Acid ◽  
Recent Work ◽  
Molecular Mechanisms ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Extracellular Stimuli

The molecular mechanisms through which extracellular stimuli mobilize intracellular Ca2+ stores are still incompletely understood. Recent work suggests that nicotinic acid–adenine dinucleotide phosphate (NAADP) can finally join the ranks of genuine Ca2+-mobilizing second messengers.

CD38 is the major enzyme responsible for synthesis of nicotinic acid–adenine dinucleotide phosphate in mammalian tissues

2002 ◽  
Vol 362 (1) ◽  
pp. 125-130 ◽  
Author(s):  
Eduardo N. CHINI ◽  
Claudia C. S. CHINI ◽  
Ichiro KATO ◽  
Shin TAKASAWA ◽  
Hiroshi OKAMOTO
Keyword(s):  
Nicotinic Acid ◽  
Knockout Mice ◽  
Second Messenger ◽  
Signalling Pathway ◽  
Rat Tissues ◽  
Mammalian Tissues ◽  
Cyclic Adp Ribose

In the present study, we have determined the role of the enzyme CD38 upon the synthesis of the Ca2+-releasing nucleotide nicotinic acid—adenine dinucleotide phosphate (NAADP). In rat tissues, we observed that the capacity for NAADP synthesis could be co-immunoprecipitated with CD38 using an anti-CD38 antibody. Furthermore, we observed that several tissues from CD38 knockout mice had no capacity for the synthesis of this nucleotide. In addition, CD38 was also identified as the major enzyme responsible for the synthesis of the second messenger cyclic ADP-ribose. These observations lead to the conclusion that CD38 is the major enzyme responsible for the synthesis of NAADP and cyclic ADP-ribose, and raises the possibility of a new signalling pathway where two different Ca2+-releasing nucleotides are synthesized by the same enzyme.

Nicotinic acid adenine dinucleotide phosphate: a new intracellular second messenger?

2002 ◽  
Vol 282 (6) ◽  
pp. C1191-C1198 ◽  
Author(s):  
Eduardo N. Chini ◽  
Frederico G. S. De Toledo
Keyword(s):  
T Cell ◽  
Nicotinic Acid ◽  
T Cell Activation ◽  
Pancreatic Secretion ◽  
Cell Activation ◽  
Second Messenger ◽  
Unanswered Question ◽  
Physiological Processes ◽  
Intracellular Ca

Nicotinic acid adenine dinucleotide phosphate (NAADP) is one of the most potent stimulators of intracellular Ca2+ release known to date. The role of the NAADP system in physiological processes is being extensively investigated at the present time. Exciting new discoveries in the last 5 years suggest that the NAADP-regulated system may have a significant role in intracellular Ca2+ signaling. The NAADP receptor and its associated Ca2+ pool have been hypothesized to be important in several physiological processes including fertilization, T cell activation, and pancreatic secretion. However, whether NAADP is a new second messenger or a tool for the discovery of a new Ca2+ channel is still an unanswered question.

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