A15

A15: Summary

The P2X7 receptor is involved in inflammation and various CNS pathologies. However, basic questions regarding its presence in different cell types as well as its molecular and physiological functions and signalling remain incompletely understood. To validate it as a drug target, we will 1) use novel P2X7-EGFP overexpressing reporter and conditional P2X7 knockout mouse models to investigate its role in macrophage-neuron interactions, 2) compare P2X7-induced signalling events in macrophages and microglia, and 3) generate P2X7-GECO construct to determine sites of P2X7- activation and it contribution to Ca2+ signalling.

Prof. Dr. Annette Nicke

Selected publications

 

  1. Leffler AE, Kuryatov A, Zebroski HA, Powell SR, Filipenko P, Hussein AK, Gorson J, Heizmann A, Lyskov S, Tsien RW, Poget SF, Nicke A, Lindstrom J, Rudy B, Bonneau R, Holford M (2017) Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models. Proc Natl Acad Sci USA 114: E8100-E8109
  2. Lörinczi É, Bhargava Y, Marino SF, Taly A, Kaczmarek-Hájek K, Barrantes-Freer A, Dutertre S, Grutter T, Rettinger J, Nicke A (2012) Involvement of the cysteine-rich “head” domain in activation and desensitization of the P2X1 receptor. Proc Natl Acad Sci USA 109:11396-11401.
  3. Schwarz N, Drouot L, Nicke A, Fliegert R, Boyer O, Guse AH, Haag F, Adriouch S, Koch-Nolte F (2012) Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS ONE 7:e41269.
  4. Nicke A, Kuan YH, Masin M, Rettinger J, Marquez-Klaka B. Bender O, Gorecki D, Murrell-Lagnado R, Soto F (2009) A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 KO mice. J Biol Chem 284:25813-25822.
  5. Marquez-Klaka, B, Rettinger J, Bhargava Y, Eisele, T, Nicke A (2007) Identification of an inter-subunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. J Neurosci 27:1456-1466.
  6. Dutertre, S*, Ulens C*, Büttner R., Fish A, van Elk, R, Kendel Y, Hopping G, Alewood PF, Schroeder C, Nicke A, Smit AB, Sixma TK, Lewis RJ (2007) AChBP-targeted α-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J 26:3858-3867.
  7. Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, Laube B (2005) The β subunit determines the ligand binding properties of synaptic glycine Receptors. Neuron 45:727-739.
  8. Nicke A, Loughnan M, Millard E, Alewood PF, Adams DJ, Daly N, Craik DJ, Lewis RJ (2003) Isolation, structure, and activity of GID, a novel α4/7-conotoxin with an additional N-terminal sequence. J Biol Chem 278:3137-3144.
  9. Horiuchi M*, Nicke A*, Gomeza J, Ashrafi A, Schmalzing G, Betz H (2001) Surface-localized glycine transporters 1 and 2 function as monomeric proteins in Xenopus oocytes. Proc Natl Acad Sci USA 98:1448-1453.
  10. Nicke A, Bäumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G (1998) P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels. EMBO J 17:3016-3028.

Prof. Dr. Annette Nicke

LMU Munich
Walther Straub Institute of Pharmacology and Toxicology
 

M.Sc. Robin Kopp

LMU Munich
Walther Straub Institute of Pharmacology and Toxicology

M.Sc. Isabel Müller

LMU Munich
Walther Straub Institute of Pharmacology and Toxicology

M.Sc. Nicolas Scalbert

LMU Munich
Walther Straub Institute of Pharmacology and Toxicology

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de