NMR spectroscopy of the neuronal tau protein: normal function and implication in Alzheimer's disease

Biochem Soc Trans. 2010 Aug;38(4):1006-11. doi: 10.1042/BST0381006.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Animals
  • Humans
  • Models, Molecular
  • Neurons / metabolism
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Phosphorylation
  • Protein Kinases / metabolism
  • tau Proteins / chemistry*
  • tau Proteins / metabolism
  • tau Proteins / physiology*

Substances

  • tau Proteins
  • Protein Kinases