Functional characterization of physiological and neurotoxic conformers of the prion protein

Principal investigator

Tatzelt, Jörg (Prof. Dr.)
Phone: +49 (0) 89 / 2180 - 75442
Fax: +49 (0) 89 / 2180 - 75415
Email:

joerg.tatzelt@med.uni-muenchen.de

Research areas

Cell biology, Biochemistry, Molecular biology

Project summary

A conformational transition of PrPC into aberrant conformers is implicated in the formation of neurotoxic and infectious PrP species. Interestingly, the physiological isoform PrPC seems to have a stress-protective activity. Our research will focus on a detailed understanding of the mechanisms by which PrPC protects from stress-induced cell death and how pathological PrP conformers induce neuronal cell death. We will define domains of PrP necessary for its stress-protective activity and search for co-factors required for signal transmission. In addition, we will investigate a possible effect of PrPSc propagation on the generation of neurotoxic PrP species in the cytosol.

Newest publications

Resenberger UK, Winklhofer KF, Tatzelt J. (2011)
Cellular Prion Protein Mediates Toxic Signaling of Amyloid Beta.
Neurodegener Dis. 2011 Dec 9. [Epub ahead of print] [PubMed]
Resenberger UK, Winklhofer KF, Tatzelt J. (2011)
Neuroprotective and Neurotoxic Signaling by the Prion Protein.
Top Curr Chem. 2011;305:101-19. [PubMed]
Resenberger UK, Harmeier A, Woerner AC, Goodman JL, Müller V, Krishnan R, Vabulas RM, Kretzschmar HA, Lindquist S, Hartl FU, Multhaup G, Winklhofer KF, Tatzelt J (2011)
The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.
EMBO J. 2011 May 18;30(10):2057-70. Epub 2011 Mar 25. Comment in: EMBO J. 2011 May 18;30(10):1882-4. [PubMed]
Sakthivelu V, Seidel RP, Winklhofer KF, Tatzelt J (2011)
Conserved stress-protective activity between prion protein and shadoo.
J Biol Chem. 2011 Mar 18;286(11):8901-8. Epub 2011 Jan 21. [PubMed]
Karpuj MV, Gelibter-Niv S, Tiran A, Rambold A, Tatzelt J, Nunziante M, Schatzl HM. (2010)
Conditional modulation of membrane protein expression in cultured cells mediated by prion protein recognition of short phosphorothioate oligodeoxynucleotides.
J Biol Chem. 2011 Mar 4;286(9):6911-7. Epub 2010 Dec 14. [PubMed]
Bouman L, Schlierf A, Lutz AK, Shan J, Deinlein A, Kast J, Galehdar Z, Palmisano V, Patenge N, Berg D, Gasser T, Augustin R, Trümbach D, Irrcher I, Park DS, Wurst W, Kilberg MS, Tatzelt J, Winklhofer KF. (2010)
Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress.
Cell Death Differ. 2011 May;18(5):769-82. Epub 2010 Nov 26. [PubMed]
Fett ME, Pilsl A, Paquet D, van Bebber F, Haass C, Tatzelt J, Schmid B, Winklhofer KF. (2010)
Parkin Is Protective against Proteotoxic Stress in a Transgenic Zebrafish Model.
PLoS One. 2010 Jul 30;5(7):e11783. [PubMed]
Schumacher MC, Resenberger U, Seidel RP, Becker CF, Winklhofer KF, Oesterhelt D, Tatzelt J, Engelhard M. (2010)
Synthesis of a GPI anchor module suitable for protein post-translational modification.
Biopolymers. 2010;94(4):457-64. [PubMed]
Ullrich S, Münch A, Neumann S, Kremmer E, Tatzelt J and Lichtenthaler SF. (2010)
The Novel Membrane Protein TMEM59 Modulates Complex Glycosylation, Cell Surface Expression and Secretion of the Amyloid Precursor Protein.
J Biol Chem. 2010 Jul 2;285(27):20664-74. Epub 2010 Apr 28. [PubMed]
Miesbauer M, Rambold AS, Winklhofer KF, Tatzelt J. (2009)
Targeting of the Prion Protein to the Cytosol: Mechanisms and Consequences.
Curr Issues Mol Biol. 2009 Sep 18;12(2):109-118. [Epub ahead of print] [PubMed]
Tatzelt J. (2009)
The Prion Protein: Friend and Foe.
Curr Issues Mol Biol. 2009 Sep 18;12(2):49-50. [Epub ahead of print] [PubMed]
Miesbauer M, Pfeiffer NV, Rambold AS, Müller V, Kiachopoulos S, Winklhofer KF, and Tatzelt J (2009)
Alpha-helical domains promote translocation of intrinsically disordered polypeptides into the endoplasmic reticulum.
J Biol Chem. 2009 Sep 4;284(36):24384-93. Epub 2009 Jun 26. [PubMed]
Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Laemmermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, Bouman L, Vogt-Weisenhorn D, Wurst W, Tatzelt J, Haass C, and Winklhofer KF (2009)
Loss of parkin or PINK1 function increases DRP1-dependent mitochondrial fragmentation.
J Biol Chem. 2009 Aug 21;284(34):22938-51. Epub 2009 Jun 22. [PubMed]
Rambold, A.S., Miesbauer, M., Olschewski, D., Riemer, C., Seidel, R., Smale, L., Brumm, L., Levy, M., Gazit, E., Oesterhelt, D., Becker, C.F.W., Engelhard E., Baier M., Winklhofer K.F. and Tatzelt J. (2008)
Green tea extracts interfere with the stress-protective activity of PrPC and the formation of PrPSc.
J Neurochem. 2008 Oct;107(1):218-29. Epub 2008 Aug 7. [PubMed]
Rambold AS, Müller V, Ron U, Ben-Tal N, Winklhofer KF, Tatzelt J (2008)
Stress-protective signalling of prion protein is corrupted by scrapie prions.
EMBO J. 2008 Jul 23;27(14):1974-84. Epub 2008 Jun 19. [PubMed]
Schlehe JS, Lutz AK, Pilsl A, Lämmermann K, Grgur K, Henn IH, Tatzelt J, Winklhofer KF (2008)
Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation.
J Biol Chem. 2008 May 16;283(20):13771-9. Epub 2008 Mar 24. [PubMed]