C-terminal truncation modulates both nucleation and extension phases of tau fibrillization

FEBS Lett. 2006 Jan 9;580(1):211-5. doi: 10.1016/j.febslet.2005.11.077. Epub 2005 Dec 12.


Proteolytic post-translational modification has been proposed as an early stage event in the aggregation of tau protein and formation of neurofibrillary lesions in Alzheimer's disease. Caspases and other proteases cleave tau in vivo at discrete locations including Asp421 and Glu391. Both cleavage products are prone to aggregation relative to wild-type, full-length tau protein. To determine the mechanism underlying this effect, the fibrillization of tau truncated after Asp421 and Glu391 residues was characterized in a full-length four-repeat tau background using quantitative electron microscopy methods under homogeneous nucleation conditions. Both C-terminal truncations decreased critical concentration relative to full-length tau, resulting in more filament mass at reaction plateau. Moreover, truncation directly augmented the efficiency of the nucleation reaction. The results suggest the mechanism through which C-terminal proteolysis can modulate tau filament accumulation depending on whether it precedes or follows nucleation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Aspartic Acid / chemistry
  • Aspartic Acid / metabolism
  • Caspases / chemistry*
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Membrane Proteins / ultrastructure
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / ultrastructure
  • Protein Processing, Post-Translational*


  • Membrane Proteins
  • Multiprotein Complexes
  • tau 40 protein, human
  • Aspartic Acid
  • Glutamic Acid
  • Caspases