title: Functional characterization of FTDP-17 tau gene mutations through their effects on Xenopus oocyte maturation.
abstract: tau gene mutations cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we have used Xenopus oocyte maturation as an indicator of microtubule function. We show that wild-type four-repeat Tau protein inhibits maturation in a concentration-dependent manner, whereas three-repeat Tau has no effect. Of the seven four-repeat Tau proteins with FTDP-17 mutations tested, five (G272V, DeltaK280, P301L, P301S, and V337M) failed to interfere significantly with oocyte maturation, demonstrating a greatly reduced ability to interact with microtubules. One mutant protein (R406W) almost behaved like wild-type Tau, and one (S305N) inhibited maturation more strongly than wild-type Tau. With the exception of R406W, wild-type Tau and all the mutants studied were similarly phosphorylated during the Xenopus oocyte maturation, and this was independent of their effects on this process. Data obtained with R406W and S305N may be related to charge changes (phosphorylation and basic amino acids). Our results demonstrate variable effects of FTDP-17 mutations on microtubules in an intact cell situation. Those findings establish Xenopus oocyte maturation as a system allowing the study of the functional effects of tau gene mutations in a quantitative manner.
authors.affiliation: INSERM U422, Institut de Médecine Prédictive et Recherche Thérapeutique, 59045 Lille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Delobel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Flament
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Ross
authors.initials: R
authors.lastname: Jakes
authors.forename: Arlette
authors.initials: A
authors.lastname: Rousseau
authors.forename: André
authors.initials: A
authors.lastname: Delacourte
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vilain
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
mesh_terms: D000818:Animals; D005260:Female; D008540:Meiosis; D008845:Microinjections; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology; D008870:Microtubules / Q000502:physiology*; D020125:Mutation, Missense; D009865:Oocytes / Q000502:physiology*; D010766:Phosphorylation; D014982:Xenopus laevis; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins