Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions

Michael Deture, Li Wen Ko, Samuel Yen, Parimala Nacharaju, Colin Easson, Jada Lewis, Marjon Van Slegtenhorst, Michael Hutton, Shu Hui Yen

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is a group of related disorders frequently characterized by the formation of tau inclusions in neurons and glial cells. To determine whether the formation of tau inclusions in FTDP-17 results from an alteration in the ability of mutant tau to maintain the microtubule (MT) system, we compared wild type four-repeat tau with three FTDP-17 mutants (P301L, V337M and R406W) for their ability to bind MT, promote MT assembly and bundling. According to in vitro binding and assembly assays, P301L is the only mutant that demonstrates a small, yet significant reduction, in its affinity for MT while both P301L and R406W have a small reduction in their ability to promote tubulin assembly. Based on studies of neuroblastoma and CHO cells transfected with GFP-tagged tau DNA constructs, both mutant and wild type tau transfectants were indistinguishable in the distribution pattern of tau in terms of co-localization with MT and generation of MT bundles. These results suggest that missense mutation of tau gene do not have an immediate impact on the integrity of MT system, and that exposure of affected neurons to additional insults or factors (e.g., aging) may be needed to initiate the formation of tau inclusions in FTDP-17. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)5-14
Number of pages10
JournalBrain Research
Volume853
Issue number1
DOIs
StatePublished - Jan 17 2000

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Keywords

  • FTDP-17
  • Microtubule assembly
  • Mutation
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Deture, M., Ko, L. W., Yen, S., Nacharaju, P., Easson, C., Lewis, J., Van Slegtenhorst, M., Hutton, M., & Yen, S. H. (2000). Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions. Brain Research, 853(1), 5-14. https://doi.org/10.1016/S0006-8993(99)02124-1