FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion

Samuel Yen, Colin Easson, Parimala Nacharaju, Michael Hutton, Shu Hui Yen

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation.

Original languageEnglish (US)
Pages (from-to)91-95
Number of pages5
JournalFEBS Letters
Volume461
Issue number1-2
DOIs
StatePublished - Nov 12 1999
Externally publishedYes

Fingerprint

Frontotemporal Dementia
Aptitude
Calpain
Missense Mutation
Digestion
Degradation
Chromosomes, Human, Pair 17
Mutation
Parkinsonian Disorders
Chromosomes
Microtubules
Neuroglia
Neurons
Dementia
Genes
Amino Acids

Keywords

  • Calpain I
  • Chromosome 17
  • Frontal temporal dementia
  • Parkinsonism
  • Tau gene

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion. / Yen, Samuel; Easson, Colin; Nacharaju, Parimala; Hutton, Michael; Yen, Shu Hui.

In: FEBS Letters, Vol. 461, No. 1-2, 12.11.1999, p. 91-95.

Research output: Contribution to journalArticle

Yen, Samuel ; Easson, Colin ; Nacharaju, Parimala ; Hutton, Michael ; Yen, Shu Hui. / FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion. In: FEBS Letters. 1999 ; Vol. 461, No. 1-2. pp. 91-95.
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