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Séminaire IBMM

Modulation by phosphorylation of Tau protein interaction with protein partners

Dr. Isabelle Landrieu, DR CNRS (NMR and Molecular Interactions, UMR 8576, CNRS, Université de Lille 1)

publié le , mis à jour le

Le Vendredi 21 octobre 2016 à 10h
UM Faculté de Pharmacie, amphithéâtre C

Aggregates of the neuronal Tau protein are found inside neurons of Alzheimer’s disease patients. Development of the disease is accompanied by increased, abnormal phosphorylation of Tau. Tau is a paradigm for the growing class of intrinsically disordered proteins, often found associated with pathologies such as neurodegenerative diseases, hence increasing the interest to understand the molecular parameters underlying their functions. In the course of our molecular investigation of Tau functions and dysfunctions in the disease, nuclear magnetic resonance (NMR) spectroscopy is used to identify the multiple phosphorylations of Tau and to characterize Tau interactions with its molecular partners. These tasks remain challenging due to Tau highly dynamical character and its 80 Ser/Thr residues, potential sites of phosphorylation that can be combined to give a multiphosphorylated Tau, leading to a very complex regulation of Tau interactions. It has proven crucial to identify phosphorylation sites to be able to link specific phosphorylations with structural or functional modifications. Functional aspects include the regulation by Tau phosphorylation of both interaction of Tau with protein partners and aggregation. The phosphorylated Tau samples characterized by NMR can be further used to decipher phospho-dependent interactions, for example with 14-3-3 proteins, and developed protein-protein interaction inhibitors.

Authors acknowledge support from TGE RMN THC (FR-3050, France) and FRABio (FR 3688, France). This study was supported by grants from the LabEx DISTALZ, ANR BinAlz and EU ITN TASPPI.

Contact local IBMM : Dr. May Morris, DR CNRS (équipe Pharmaco Cellulaire)


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