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Ca 2+ and Mg 2+ selectively induce aggregates of PHF‐tau but not normal human tau
Author(s) -
Yang Liangsheng,
KsiezakReding Hanna
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990101)55:1<36::aid-jnr5>3.0.co;2-e
Subject(s) - chemistry , neurodegeneration , tau protein , gel electrophoresis , protein aggregation , polyacrylamide gel electrophoresis , biophysics , phosphorylation , biochemistry , microbiology and biotechnology , alzheimer's disease , biology , pathology , enzyme , medicine , disease
The molecular mechanism of pathological aggregation of microtubule‐associated protein tau during neurodegeneration is unclear. In the present study, the in vitro effect of various metal ions on the aggregation of tau was examined using paired helical filament tau (PHF‐tau) obtained from corticobasal degeneration (CBD) and Alzheimer's disease (AD) brains as well as normal human tau proteins isolated from fetal and adult brains and a recombinant system. Among the metal ions tested, Ca 2+ and Mg 2+ effectively induced formation of approximately 340 kD aggregates of PHF‐tau but not normal tau proteins as determined by sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis and immunoblotting. Al 3+ and Fe 2+ precipitated both PHF‐tau and normal tau protein as SDS‐insoluble pellets. The other metal ions examined (Cu 2+ , Zn 2+ , and Li + ) were inactive and caused neither aggregation nor precipitation of any tau protein. Intermixing experiments using PHF‐tau and various normal tau preparations showed that the 340‐kD aggregates induced by Ca 2+ contained PHF‐tau but not normal tau regardless whether unmodified (recombinant) or highly phosphorylated (fetal brain) tau proteins were used. The present results suggest that post‐translational modifications other than the fetal‐type phosphorylation are required for Ca 2+ ‐ and Mg 2+ ‐dependent aggregation of PHF‐tau and that the regional elevation of these ions may trigger pathological deposition of PHF‐tau in certain neurodegenerative disorders. J. Neurosci. Res. 55:36–43, 1999. © 1999 Wiley‐Liss, Inc.