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.
Thanks to the support from the Deutsche Forschungsgesellschaft (DFG) we are eager to go from the formation of Ca2+ microdomains to the analysis of Ca2+ nanodomains with a new Superresolution Spinning-disk microscope!
For further announcements see:
Parys JB, Guse AH. Full focus on calcium. Sci Signal. 2019 Sep 17;12(599). pii: eaaz0961.
Jimenez-Mateos EM, Smith J, Nicke A, Engel T. Regulation of P2X7 receptor expression and function in the brain. Brain Res Bull. 2019 Sep;151:153-163.
Koch-Nolte F, Eichhoff A, Pinto-Espinoza C, Schwarz N, Schäfer T, Menzel S, Haag F, Demeules M, Gondé H, Adriouch S. Novel biologics targeting the P2X7 ion channel. Curr Opin Pharmacol. 2019 Aug;47:110-118.
Kopp R, Krautloher A, Ramírez-Fernández A, Nicke A. P2X7 Interactions and Signaling - Making Head or Tail of It. Front Mol Neurosci. 2019 Aug 7;12:183.
Schneider E, Rissiek A, Winzer R, Puig B, Rissiek B, Haag F, Mittrücker HW, Magnus T, Tolosa E. Generation and Function of Non-cell-bound CD73 in Inflammation. Front Immunol. 2019 Jul 26;10:1729.