SFB1328

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.

LATEST PUBLICATION

Josts, I., Veith, K. & Tidow, H. Ternary structure of the outer membrane transporter FoxA provides insights into TonB-mediated siderophore uptake. eLife 8, e48528 (2019)

Johnsen B, Kaschubowski KE, Nader S, Schneider E, Nicola JA, Fliegert R, Wolf IMA, Guse AH, Nikolaev VO, Koch-Nolte F, Haag F. P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP. Purinergic Signal. 2019 Apr 23

Rotermund N, Schulz K, Hirnet D, Lohr C. Purinergic Signaling in the Vertebrate Olfactory System. Front Cell Neurosci. 2019 Apr 16;13:112.

J. Harberts, R. Zierold, C. Fendler, A. Koitmäe, P. Bayat, I. Fernandez-Cuesta, G. Loers, B.-P. Diercks, R. Fliegert, A.H. Guse, C. Ronning, G. Otnes, M. Borgström, R.H. Blick, Culturing and patch clamping of Jurkat T cells and neurons on Al ₂ O ₃ coated nanowire arrays of altered morphology, RSC Adv. 9 (2019) 11194–11201.

Baszczyňski O, Watt JM, Rozewitz MD, Guse AH, Fliegert R, Potter BVL. Synthesis of terminal ribose analogues of adenosine 5'-diphosphate ribose (ADPR) as probes for the Transient Receptor Potential (TRP) cation channel TRPM2. J Org Chem. 2019 Apr 12.