MASTER-NAADP: a membrane permeable precursor of the Ca2+ mobilizing second messenger NAADP
Upon stimulation of membrane receptors, nicotinic acid adenine dinucleotide phosphate (NAADP) is formed as second messenger within seconds and evokes Ca<sup>2+</sup> signaling in many different cell types. Here, to directly stimulate NAADP signaling, MASTER-NAADP, a Membrane permeAble, STabilized, bio-rEversibly pRotected precursor of NAADP is synthesized and release of its active NAADP mimetic, benzoic acid C-nucleoside, 2'-phospho-3'F-adenosine-diphosphate, by esterase digestion is confirmed. In the presence of NAADP receptor HN1L/JPT2 (hematological and neurological expressed 1-like protein, HN1L, also known as Jupiter microtubule-associated homolog 2, JPT2), this active NAADP mimetic releases Ca<sup>2+</sup> and increases the open probability of type 1 ryanodine receptor. When added to intact cells, MASTER-NAADP initially evokes single local Ca<sup>2+</sup> signals of low amplitude. Subsequently, also global Ca<sup>2+</sup> signaling is observed in T cells, natural killer cells, and Neuro2A cells. In contrast, control compound MASTER-NADP does not stimulate Ca<sup>2+</sup> signaling. Likewise, in cells devoid of HN1L/JPT2, MASTER-NAADP does not affect Ca<sup>2+</sup> signaling, confirming that the product released from MASTER-NAADP is a bona fide NAADP mimetic.
Authors
- Berit Troost
- Mariella Weiß (ORCID: https://orcid.org/0000-0002-7433-6805)
- Volodymyr Tsvilovskyy (ORCID: https://orcid.org/0000-0003-1275-3029)
- René Werner (ORCID: https://orcid.org/0000-0002-2296-3305)
- Mikołaj Nawrocki (ORCID: https://orcid.org/0000-0002-8579-7236)
- Andreas H. Guse (ORCID: https://orcid.org/0000-0002-3972-401X)
- Lena-Marie Woelk
- Marcus Altfeld (ORCID: https://orcid.org/0000-0001-5972-2997)
- Patrick Dekiert
- Imrankhan Khansahib (ORCID: https://orcid.org/0000-0001-5062-6499)
- Oliver B. Clarke (ORCID: https://orcid.org/0000-0003-1876-196X)
- Viviana Granato (ORCID: https://orcid.org/0000-0002-8150-4889)
- Chris Meier (ORCID: https://orcid.org/0000-0002-8323-5635)
- Björn‐Philipp Diercks (ORCID: https://orcid.org/0000-0002-6635-1706)
- Rebekka Medert (ORCID: https://orcid.org/0000-0001-7571-3732)
- Marc Freichel (ORCID: https://orcid.org/0000-0003-1387-2636)
- Kai J Winterberg (ORCID: https://orcid.org/0000-0001-5126-5525)
- Dejan Kovacevic
- Franziska Möckl
- Samuel Huber (ORCID: https://orcid.org/0000-0001-9325-8227)
- Fynn Gerlach
- Huan Li (ORCID: https://orcid.org/0000-0001-6518-8591)
- Melanie Hofmann
- Sarah Krukenberg
- Tobis Hub
- M. A. Hinrichs
- Fritz Förster
Institutions
- Universität Hamburg (DE)
- Heidelberg University (DE)
- Columbia University Irving Medical Center (US)
- University Medical Center Hamburg-Eppendorf (DE)
- German Centre for Cardiovascular Research (DE)
- Columbia University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s41467-024-52024-y
- Citations
- 6
- Primary Topic
- Calcium signaling and nucleotide metabolism
- Type
- article
- Field-Weighted Citation Impact
- 2.41
Funders
- Deutsche Forschungsgemeinschaft
- Jung-Stiftung für Wissenschaft und Forschung