| Autor: |
Sarah Krukenberg, Franziska Möckl, Mariella Weiß, Patrick Dekiert, Melanie Hofmann, Fynn Gerlach, Kai J. Winterberg, Dejan Kovacevic, Imrankhan Khansahib, Berit Troost, Macarena Hinrichs, Viviana Granato, Mikolaj Nawrocki, Tobis Hub, Volodymyr Tsvilovskyy, Rebekka Medert, Lena-Marie Woelk, Fritz Förster, Huan Li, René Werner, Marcus Altfeld, Samuel Huber, Oliver Biggs Clarke, Marc Freichel, Björn-Philipp Diercks, Chris Meier, Andreas H. Guse |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-52024-y |
| Popis: |
Abstract Upon stimulation of membrane receptors, nicotinic acid adenine dinucleotide phosphate (NAADP) is formed as second messenger within seconds and evokes Ca2+ 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 Ca2+ and increases the open probability of type 1 ryanodine receptor. When added to intact cells, MASTER-NAADP initially evokes single local Ca2+ signals of low amplitude. Subsequently, also global Ca2+ signaling is observed in T cells, natural killer cells, and Neuro2A cells. In contrast, control compound MASTER-NADP does not stimulate Ca2+ signaling. Likewise, in cells devoid of HN1L/JPT2, MASTER-NAADP does not affect Ca2+ signaling, confirming that the product released from MASTER-NAADP is a bona fide NAADP mimetic. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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