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 (*equal contribution)

Jooss T*, Zhang J*, Zimmer B, Rezzonico-Jost T, Rissiek B, Felipe Pelczar P, Seehusen F, Koch-Nolte F, Magnus T, Zierler S, Huber S, Schemann M, Grassi F, Nicke A. Macrophages and glia are the dominant P2X7-expressing cell types in the gut nervous system - no evidence for a role of neuronal P2X7 receptors in colitis. Mucosal Immunol. (2023) Jan 9:S1933-0219(22)01729-9.
Durner A, Durner E, Nicke A. Improved ANAP incorporation and VCF analysis reveals details of P2X7 current facilitation and a limited conformational interplay between ATP binding and the intracellular ballast domain. Elife. (2023) Jan 4;12:e82479.
Beamer E, Morgan J, Alves M, Menéndez Méndez A, Morris G, Zimmer B, Conte G, de Diego-Garcia L, Alarcón-Vila C, Yiu Ng NK, Madden S, Calzaferri F, de Los Ríos C, García AG, Hamacher M, Dinkel K, Pelegrín P, Henshall DC, Nicke A, Engel T. Increased expression of the ATP-gated P2X7 receptor reduces responsiveness to anti-convulsants during status epilepticus in mice. Br J Pharmacol. (2022) Jun;179(12):2986-3006.
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. Deviant reporter expression and P2X4 passenger gene overexpression in the soluble EGFP BAC transgenic P2X7 reporter mouse model. Sci Rep (2020) 10:19876.
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.
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. Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody. Elife (2018) 7:e36217.
Lörinczi É, Bhargava Y, Marino SF, Taly A, Kaczmarek-Hájek K, Barrantes-Freer A, Dutertre S, Grutter T, Rettinger J, Nicke A. Involvement of the cysteine-rich “head” domain in activation and desensitization of the P2X1 receptor. Proc Natl Acad Sci USA (2012) 109:11396-11401.
Nicke A, Kuan YH, Masin M, Rettinger J, Marquez-Klaka B. Bender O, Gorecki D, Murrell-Lagnado R, Soto F. A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 KO mice. J Biol Chem (2009) 284:25813-25822.
Marquez-Klaka, B, Rettinger J, Bhargava Y, Eisele, T, Nicke A. Identification of an inter-subunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. J Neurosci (2007) 27:1456-1466.
Nicke A, Bäumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G. P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels EMBO J (1998) 17, 3016-3028.