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Imaging Initial Ca2+ Microdomains in Primary T Cells
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NAADP: a universal Ca2+ trigger.

Andreas H Guse1, Hon Cheung Lee

  • 1The Calcium Signaling Group, Institute of Biochemistry and Molecular Biology I, Cellular Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20146 Hamburg, Germany. guse@uke.uni-hamburg.de

Science Signaling
|November 6, 2008
PubMed
Summary
This summary is machine-generated.

Nicotinic acid adenine dinucleotide phosphate (NAADP) initiates calcium signals in cells, targeting acidic and endoplasmic reticulum stores. Its metabolism by CD38 is key to understanding this vital calcium signaling pathway.

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Signaling

Background:

  • Cells utilize multiple calcium ion (Ca2+) stores and messengers like IP(3) and cADPR.
  • Nicotinic acid adenine dinucleotide phosphate (NAADP) is a recently identified Ca2+-mobilizing messenger acting across diverse cell types.
  • NAADP is known to target acidic (lysosome-like) and endoplasmic reticular Ca2+ stores.

Purpose of the Study:

  • To elucidate the role of NAADP in initiating and amplifying Ca2+ signals.
  • To understand the mechanism of NAADP metabolism by the enzyme CD38.
  • To identify key components of the NAADP-mediated Ca2+ signaling pathway.

Main Methods:

  • Review of accumulating evidence on NAADP targeting of Ca2+ stores.
  • Analysis of recent studies on NAADP's role in initiating Ca2+ signals.
  • Examination of the determined crystal structure of CD38 and its substrate complexes.

Main Results:

  • NAADP initiates Ca2+ signals, which are amplified by cADPR or IP(3) through Ca2+-induced Ca2+ release.
  • Diverse stimuli rapidly increase endogenous NAADP concentration within seconds.
  • CD38 catalyzes both synthesis and hydrolysis of NAADP, facilitating its rapid metabolism.
  • The crystal structure of CD38 clarifies its multifunctional catalytic mechanism.

Conclusions:

  • Advances in understanding CD38 structure and function are crucial for deciphering NAADP signaling.
  • Further research is expected to reveal all components of the NAADP-mediated Ca2+ signaling pathway.
  • NAADP plays a fundamental role in cellular calcium homeostasis and signaling.