NMR spectroscopy of the neuronal tau protein: normal function and implication in Alzheimer's disease.
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.
Landrieu
Isabelle
I
CNRS-UMR 8576 - IFR 147, Lille 1 Science and Technology University, 59655 Villeneuve d'Ascq Cedex, France. isabelle.landrieu@univ-lille1.fr
Leroy
Arnaud
A
Smet-Nocca
Caroline
C
Huvent
Isabelle
I
Amniai
Laziza
L
Hamdane
Malika
M
Sibille
Nathalie
N
Buée
Luc
L
Wieruszeski
Jean-Michel
JM
Lippens
Guy
G
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D016875:tau Proteins; D011494:Protein Kinases