A15: SFB 1328

A15 Project movie

A15

Activation of the pro-inflammatory P2X7 receptor induces diverse cellular responses. Using in situ cross-linking and mass spectrometry we have identified a range of potential interactors. We now aim to use our P2X7-EGFP mouse model in combination with biochemical and biophysical approaches to (i) define the role of P2X7 in cell migration and validate further interaction partners, (ii) elucidate cell type-specific P2X7 signaling pathways, (iii) determine the respective protein interaction sites and dynamics, and (iv) identify the binding sites and mode of action of P2X7-specific modulatory nanobodies.

Prof. Dr. Annette Nicke

E-Mail: annette.nicke©lrz.uni-muenchen.de
www: Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-MaximiliansUniversität

Prof. Dr. Annette Nicke

Selected publications

Ramírez-Fernández A, Urbina-Treviño L, Conte G, Alves M, Rissiek B, Durner A, Scalbert N, Zhang J, Magnus T, Koch-Nolte F, Plesnila N, Deussing JM, Engel T, Kopp R, Nicke A (2020) Deviant reporter expression and P2X4 passenger gene overexpression in the soluble EGFP BAC transgenic P2X7 reporter mouse model. Sci Rep 10:19876
Kaczmarek-Hajek K, Zhang J, Kopp R, Grosche A, Rissiek B, Saul A, Bruzzone S, Engel T, Jooss T, Krautloher A, Schuster S, Magnus T, Stadelmann C, Sirko S, Koch-Nolte F, Eulenburg V, Nicke A (2018) Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody. Elife 7:e36217
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.
Beissner M*, Dutertre S*, Schemm R*, Danker T, Sporning A, Grubmüller H, Nicke A(2012) Efficient binding of 4/7 α-conotoxins to nicotinic α4β2 receptors is prevented by R185 and P195 in the α4 subunit Mol Pharmacol 82, 711-718
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.
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.
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.
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.
Horiuchi M*, Nicke A*, Gomeza J, Ashrafi A, Schmalzing G, Betz H. Surface-localized glycine transporters 1 and 2 function as monomeric proteins in Xenopus oocytes. Proc Natl Acad Sci USA 98, 1448-1453.
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.