Promotion and stabilization of microtubule self-assembly by disulfide cross-linked TAU-TAU dimers and MAP2-MAP2 dimers

Daniel L. Purich, L. DiNoto, Michael Deture

Research output: Contribution to journalArticle

Abstract

The microtubule-associated proteins TAU and MAP2 use their highly related C-terminal microtubule-binding regions (MTBRs) to interact with microtubules (MTs) as well as actin and intermediate filaments. TAU-MTBR has hoen directly isolated from pronase treated Alzheimer Paired Helical Filaments (PHFs), and we recently demonstrated that MAP2 MTBR and MAP2c ran polymerize in vitro to form straight filaments (SFs). TAU and MAP2 form disulfide-linked homodimers as an early step in SF/PHF assembly, and the critical thiol group lies within the middle repeat sequence which is directly engaged in MT binding. This raises the question of whether disulfide formation blocks microtubuie binding, thereby diverting TAU-TAU or MAP2-MAP2 dimers toward PHF or SF formation. We now report (a) cross-linked TAU dimers and MAP'2 dimers can indeed promote tubulin polymerization; (b) dimers bind to MTs at physiological salt concentration; and (V) dimer affinity for MTs equals, or is slighly less than, that of their monomeric forms. Disulfide cross-linking does not impair TAU or MAP2 interactions with lubulin or MTs, suggesting PHI' formation in Alzheirner's Disease probably requires more than just a pool of cross-linked dimers.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998
Externally publishedYes

Fingerprint

sulfides
Microtubules
Disulfides
Dimers
Self assembly
microtubules
Stabilization
Pronase
Microtubule-Associated Proteins
Tubulin
Sulfhydryl Compounds
Intermediate Filaments
Actins
intermediate filaments
Salts
Actin Cytoskeleton
Polymerization
tubulin
microfilaments
thiols

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Promotion and stabilization of microtubule self-assembly by disulfide cross-linked TAU-TAU dimers and MAP2-MAP2 dimers. / Purich, Daniel L.; DiNoto, L.; Deture, Michael.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

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