PMID- 11756436
OWN - NLM
STAT- MEDLINE
DCOM- 20020405
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 11
DP  - 2002 Mar 15
TI  - Functional characterization of FTDP-17 tau gene mutations through their effects 
      on Xenopus oocyte maturation.
PG  - 9199-205
AB  - 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.
FAU - Delobel, Patrice
AU  - Delobel P
AD  - INSERM U422, Institut de Medecine Predictive et Recherche Therapeutique, 59045 
      Lille, France.
FAU - Flament, Stephane
AU  - Flament S
FAU - Hamdane, Malika
AU  - Hamdane M
FAU - Jakes, Ross
AU  - Jakes R
FAU - Rousseau, Arlette
AU  - Rousseau A
FAU - Delacourte, Andre
AU  - Delacourte A
FAU - Vilain, Jean-Pierre
AU  - Vilain JP
FAU - Goedert, Michel
AU  - Goedert M
FAU - Buee, Luc
AU  - Buee L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20011226
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (MAPT protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Animals
MH  - Female
MH  - Meiosis
MH  - Microinjections
MH  - Microtubule-Associated Proteins/*genetics/physiology
MH  - Microtubules/*physiology
MH  - *Mutation, Missense
MH  - Oocytes/*physiology
MH  - Phosphorylation
MH  - Xenopus laevis
MH  - tau Proteins/*genetics
EDAT- 2002/01/05 10:00
MHDA- 2002/04/06 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/04/06 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - S0021-9258(19)36289-1 [pii]
AID - 10.1074/jbc.M107716200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Mar 15;277(11):9199-205. doi: 10.1074/jbc.M107716200. Epub 2001 
      Dec 26.