Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments

Neuron. 1993 Jun;10(6):1151-60. doi: 10.1016/0896-6273(93)90063-w.

Abstract

We have investigated ubiquitinated paired helical filaments, which produce a proteinaceous smear in SDS-polyacrylamide gel electrophoresis and immunoblotting. The smear consisted largely of the carboxy-terminal portion of tau and ubiquitin. The ubiquitin-targeted protein was identified as tau in paired helical filaments, and the conjugation sites were localized to the microtubule-binding region. Most ubiquitin in paired helical filaments occurred as a monoubiquitinated form, and only a small proportion of ubiquitin formed multiubiquitin chains. There was a ubiquitin-negative smear, in which tau was much less processed in the amino-terminal portion. This strongly suggests that the amino-terminal processing of tau in paired helical filaments precedes its ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Endopeptidases
  • Humans
  • Mass Spectrometry
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Neurofibrillary Tangles / metabolism
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism*
  • Peptide Mapping
  • Protein Binding
  • Ubiquitins / isolation & purification
  • Ubiquitins / metabolism*
  • tau Proteins / isolation & purification
  • tau Proteins / metabolism*

Substances

  • Antibodies, Monoclonal
  • Peptide Fragments
  • Ubiquitins
  • tau Proteins
  • Endopeptidases