1. NMR spectroscopy of the neuronal tau protein: normal function and implication in Alzheimer's disease
- Author
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Arnaud Leroy, Isabelle Huvent, Luc Buée, Isabelle Landrieu, Malika Hamdane, Guy Lippens, Caroline Smet-Nocca, Laziza Amniai, Jean-Michel Wieruszeski, Nathalie Sibille, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine
- Subjects
Models, Molecular ,Tau protein ,MESH: Neurons ,tau Proteins ,Isomerase ,Proteomics ,Biochemistry ,03 medical and health sciences ,Alzheimer Disease ,MESH: Nuclear Magnetic Resonance, Biomolecular ,Animals ,Humans ,MESH: Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Phosphorylation ,MESH: Protein Kinases ,Nuclear Magnetic Resonance, Biomolecular ,030304 developmental biology ,chemistry.chemical_classification ,Neurons ,0303 health sciences ,MESH: Humans ,MESH: Phosphorylation ,biology ,Kinase ,030302 biochemistry & molecular biology ,Nuclear magnetic resonance spectroscopy ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,MESH: tau Proteins ,Amino acid ,chemistry ,PIN1 ,biology.protein ,Protein Kinases ,MESH: Alzheimer Disease ,MESH: Models, Molecular - Abstract
International audience; NMR spectroscopy was used to explore the different aspects of the normal and pathological functions of tau, but proved challenging because the protein contains 441 amino acids and has poor signal dispersion. We have set out to dissect the phosphorylation patterns of tau in order to understand better its role in the aggregation process and microtubule-binding regulation. Our current knowledge on the functional consequences of specific phosphorylations is still limited, mainly because producing and assessing quantitatively phosphorylated tau samples is far from straightforward, even in vitro. We use NMR spectroscopy as a proteomics tool to characterize the phosphorylation patterns of tau, after in vitro phosphorylation by recombinant kinases. The phosphorylated tau can next be use for functional assays or interaction assays with phospho-dependent protein partners, such as the prolyl cis-trans isomerase Pin1.
- Published
- 2010