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Yann Fichou, 3 May 2018, 2pm, IECB Internal CBMN seminars: Alexandre Ciaccafava and Guillaume Compain, 5 April 2018 Alain Roussel, 29/03/2018, 4 pm, ENSCBP Simon Poly, 22 march 2018, 2pm, ENSCBP J.Crassous, M. Sallé & A. Martinez, 18/12/2017, 10 am, IECB O.Reinaud & V. Artero, 7/12/2017, 10 am, IECB R. Dos santos Morais, 30/11/2017, 4 PM, ENSCBP Christian Griesinger, November 24th, 11am, IECB Takahiro Muraoka, 16/11/2017, 11am, ENSCBP Vladimir Torbeev, 9/11/2017, 2pm, ENSCBP M. D. Smith & T.Constantieux, 3/11/2017, 2h30 pm, IECB James Nowick, 15 september 2017, 11am, IECB Emmanuelle Thinon, 28 June 2017, 11 am, IECB Caroline Tokarski, 15 June 2017, 4pm, ENSCBP Christian Salesse, 8 June 2017, 4pm, ENSCBP Patrice Rey, 01 June 2017, 2h30 pm, ENSCBP Christina Sizun, 18 May 2017, 4 pm, ENSCBP Marisela Velez, 5 May 2017, 11am, IECB Iqbal Choudhary, 27 April 2017, 4 pm, ENSCBP Vincent Aucagne, 21 April 2017, 11 am, IECB Sophie Zinn-Justin, 14 April 2017, 11 am, IECB Cécile Feuillie, 16 February 2017, 4 PM, ENSCBP Félix M. Goñi, 8 december 2016, 4 pm, ENSCBP Félix M. Goñi, 17 november 2016, 4 pm, ENSCBP Carl Creutz, 20 october 2016, 4 pm, ENSCBP Diego Romero, 30 september 2016, 11 am, IECB A. Ciaccafava, 8 september 2016, 14h, ENSCBP A. Ramamoorthy, 16 June 2016, 16h, ENSCBP Alexandre de Brevern, 2 june 2016, ENSCBP Isabelle Landrieu, 26 May, 16h, ENSCBP Frances Sepavoric, 12 May, 16h, ENSCBP Thomas Pradeu, 7 April 2016, 9h, ENSCBP Françoise Argoul, 3 march 2016, 16h, ENSCBP Corinne Loutelier-Bourhis, 16/12/2015, 16h Aristotelis XENAKIS, 3 december 2015, 16h Fabian Kiessling, 26 november 2015, 11h Michaël Molinari, 20 november 2015, 11h Dipankar Das Sarma, 28 October 2015, 14h. Olivier Donard, 22 october 2015, 16h, ENSCBP E. Morvan & A.Grelard, 17/12/2015, 16h, ENSCBP Christophe Cullin, 10 september 2015, 14 h Brigitte Lindet, 18 June 2015, 16h, ENSCBP(B) Marion Decossas, 4 June 2015, 16h, ENSCBP(B) Pascale Schellenberger, 21 Mai 2015, 16h F. Leal-Calderon, 7 May 2015, 16h, ENSCBP(B) Ibrahim Abdulhalim, 9 April 2015, 14h, ENSCBP Manon Carré, 26 March 2015, 14h, ENSCBP(B) C. Bure & JM Schmitter, 19 March 2015, 16h T. Ogata & H. Ihara, 17 March 2015, 11h, IECB Banafshe Larijani, 12 March 2015, 16h, ENSCBP
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Yann Fichou, 3 May 2018, 2pm, IECB Internal CBMN seminars: Alexandre C... Alain Roussel, 29/03/2018, 4 pm, EN... Simon Poly, 22 march 2018, 2pm, ENS... J.Crassous, M. Sallé & A. Martinez... O.Reinaud & V. Artero, 7/12/2017, 1... R. Dos santos Morais, 30/11/2017, 4... Christian Griesinger, November 24th... Takahiro Muraoka, 16/11/2017, 11am,... Vladimir Torbeev, 9/11/2017, 2pm, E... M. D. Smith & T.Constantieux, 3/11/... James Nowick, 15 september 2017, 11... Emmanuelle Thinon, 28 June 2017, 11... Caroline Tokarski, 15 June 2017, 4p... Christian Salesse, 8 June 2017, 4pm... Patrice Rey, 01 June 2017, 2h30 pm,... Christina Sizun, 18 May 2017, 4 pm,... Marisela Velez, 5 May 2017, 11am, I... Iqbal Choudhary, 27 April 2017, 4 p... Vincent Aucagne, 21 April 2017, 11 ... Sophie Zinn-Justin, 14 April 2017, ... Cécile Feuillie, 16 February 2017,... Félix M. Goñi, 8 december 2016, 4... Félix M. Goñi, 17 november 2016, ... Carl Creutz, 20 october 2016, 4 pm,... Diego Romero, 30 september 2016, 11... A. Ciaccafava, 8 september 2016, 14... A. Ramamoorthy, 16 June 2016, 16h,... Alexandre de Brevern, 2 june 2016, ... Isabelle Landrieu, 26 May, 16h, ENS... Frances Sepavoric, 12 May, 16h, ENS... Thomas Pradeu, 7 April 2016, 9h, EN... Françoise Argoul, 3 march 2016, 1... Corinne Loutelier-Bourhis, 16/12/20... Aristotelis XENAKIS, 3 december 201... Fabian Kiessling, 26 november 2015,... Michaël Molinari, 20 november 2015... Dipankar Das Sarma, 28 October 2015... Olivier Donard, 22 october 2015, 16... E. Morvan & A.Grelard, 17/12/2015, ... Christophe Cullin, 10 september 201... Brigitte Lindet, 18 June 2015, 16h,... Marion Decossas, 4 June 2015, 16h, ... Pascale Schellenberger, 21 Mai 2015... F. Leal-Calderon, 7 May 2015, 16h, ... Ibrahim Abdulhalim, 9 April 2015, 1... Manon Carré, 26 March 2015, 14h, ... C. Bure & JM Schmitter, 19 March 20... T. Ogata & H. Ihara, 17 March 2015,... Banafshe Larijani, 12 March 2015, 1...
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Patricia DULOR Anthony BOUTER Olivier LAMBERT Jochen LANG Pascale SUBRA-PATERNAULT Maria URDACI Marie-Christine DURRIEU Xavier SANTARELLI Gilles GUICHARD Yann FERRAND Isabelle BESTEL Juan ELEZGARAY Antoine LOQUET Sophie LECOMTE Reiko ODA Marc BONNEU

Yann Fichou, 3 May 2018, 2pm, IECB

The seminar  will take place the 3rd of May 2018, at 2pm in the IECB amphitheatre, 2 rue Robert Escarpit Pessac.

 

From solution tau to amyloid aggregates: pathway matters a great deal

 

Yann Fichou1, Michael Vigers1, Yanxian Lin1, Andrew K. Goring1, Neil A. Eschmann1, Songi Han1

 

1Department of chemistry, University of California Santa Barbara, USA

 

  Abstract

  The intrinsically disordered tau protein is known to aggregate into amyloid filaments involved in many neurodegenerative diseases, including Alzheimer’s disease (AD) and Frontotemporal dementia (FTD). Different types of aggregates, called strains, are thought to be involved in distinct pathologies and to faithfully propagate by converting naïve monomers, recalling a prion-like behavior. Yet, there is no structural basis for this seed-assisted conversion and for the selection of well-define strain. In this presentation, I will provide new insights into tau aggregation pathways by using complementary biophysical methods, including electron paramagnetic resonance spectroscopy (EPR).

 

  Most of the studies aiming at understanding tau aggregation mechanisms and driving forces have been carried out using heparin to trigger recombinant tau aggregation. This protocol was thought to create a model aggregate for AD filaments.

 

  I will show that polyanions, such as heparin or RNA, act as a brace that converts functional tau into aggregation-prone conformers. We argue that disease mutations, such P301L, shift the conformational ensemble toward pathological conformers, thereby facilitating the initial conformational rearrangement that triggers the aggregation cascade. However, because polyanions are unstructured polymers, they provide a poor scaffold for filament formation, resulting in imperfectly packed amyloid aggregates. This mispacking has strong consequences on the properties of the mature fibers. We show that upon removal of the cofactors (Heparin or RNA), tau monomers spontaneously disassemble from mature fibers and lose their aggregation-prone conformation. 

 

  In addition, I will show that heparin-induced filaments are drastically different from brain-extracted AD filaments. On the one hand, the main structural features of AD filaments are not reproduced by heparin aggregates. On the other hand, even when embedded in amyloid fibers, the tau protein exists in heterogeneous conformations, showing that heparin is incapable of selecting a pathway toward a given strain. We suggest this is the main reason why heparin-induced filaments have poor seeding capacity.

 

  We argue that the quality of amyloid aggregates, i.e. the packing and conformations of the monomeric subunits, is a predominant factor that control their properties and therefore their biological relevance.

 

Contact: Antoine Loquet, a.loquet@iecb.u-bordeaux.fr

 

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