Extracellular and intracellular adenine nucleotides (AN) impact on all central processes in biology and medicine. AN are essential and ubiquitous signaling molecules involved in regulating universal cellular processes, including (i) cell-cell communication and (ii) intracellular signaling.
Unresolved issues regarding the signaling function of extracellular AN in inflammation, e.g. adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD), relate to the timing and location of their release, their conversion by ecto-enzymes, and their biological role within the balance of inflammatory processes. Likewise, the precise role of intracellular AN second messengers, e.g. nicotinic acid adenine dinucleotide phosphate (NAADP) or 3’,5’-cyclic adenosine monophosphate (cAMP), in the spatio-temporal control of signaling processes by forming or modulating microdomains with their metabolizing enzymes, specific binding proteins or receptors, or target ion channels remains largely unknown.
The central goal of the research consortium is to further our understanding of the regulatory roles of AN and their kinetics in the context of inflammatory diseases. Specific aims relate to (i) modulation of the balance between pro- and anti-inflammatory processes by AN converting ecto-nucleotidases and purinergic receptors, and to (ii) AN-driven intracellular calcium signaling and cAMP signaling in inflammation.
Congratulations to Christa Müller (A11) who has been named editor in chief of ACS Pharmacology & Translational Science. “The journal will set new standards in the field and support diversity, and emerging young scientists will be invited to play an active role,” Müller says.
PAPER SCIENCE SIGNALING
Although NAADP was discovered already over 25 years ago, as the most potent Ca2+ mobilizing messenger, the mechanism of action is still unclear. In this SFB publication, we present a long-assumed binding protein for NAADP called Hn1l/Jpt2, which has essential role in activating primary T cells, hence the adaptive immune response.
For further announcements see:
Hadaeghi F, Diercks BP, Schetelig D, Damicelli F, Wolf IMA, Werner R. Spatio-temporal feature learning with reservoir computing for T-cell segmentation in Ca2+ live-cell fluorescence microscopy. Sci Rep. 2021 Apr 15;11(1):8233.
Roggenkamp HG, Khansahib I, Hernandez C LC, Zhang Y, Lodygin D, Krüger A, Gu F, Möckl F, Löhndorf A, Wolters V, Woike D, Rosche A, Bauche A, Schetelig D, Werner R, Schlüter H, Failla AV, Meier C, Fliegert R, Walseth TF, Flügel A, Diercks BP, Guse AH (2021) HN1L/JPT2: A signaling protein that connects NAADP generation to Ca 2+ microdomain formation. Sci Signal 14(675):eabd5647
Diercks BP, Jensen HH, Chalmers SB, Coode E, Vaughan MB, Tadayon R, Sáez PJ, Davis FM, Brohus M (2021) The first junior European calcium society meeting: Calcium research across scales, kingdoms and countries. Biochim Biophys Acta Mol Cell Res 1868:118999
Fischer T, Prey J, Eschholz L, Rotermund N, Lohr C (2021) Norepinephrine-Induced Calcium Signaling and Store-Operated Calcium Entry in Olfactory Bulb Astrocytes. Front Cell Neurosci 15:639754
Schaltenberg N, John C, Heine M, Haumann F, Rinninger F, Scheja L, Heeren J, Worthmann A (2021) Endothelial Lipase Is Involved in Cold-Induced High-Density Lipoprotein Turnover and Reverse Cholesterol Transport in Mice. Front Cardiovasc Med 8:628235