PMID- 10627302
OWN - NLM
STAT- MEDLINE
DCOM- 20000307
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 853
IP  - 1
DP  - 2000 Jan 17
TI  - Missense tau mutations identified in FTDP-17 have a small effect on 
      tau-microtubule interactions.
PG  - 5-14
AB  - 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.
FAU - DeTure, M
AU  - DeTure M
AD  - Departments of Pharmacology, Biochemistry and Molecular Biology, Birdsall Medical 
      Research Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, 
      FL 32224, USA.
FAU - Ko, L W
AU  - Ko LW
FAU - Yen, S
AU  - Yen S
FAU - Nacharaju, P
AU  - Nacharaju P
FAU - Easson, C
AU  - Easson C
FAU - Lewis, J
AU  - Lewis J
FAU - van Slegtenhorst, M
AU  - van Slegtenhorst M
FAU - Hutton, M
AU  - Hutton M
FAU - Yen, S H
AU  - Yen SH
LA  - eng
GR  - AG01136/AG/NIA NIH HHS/United States
GR  - NS37143/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tubulin)
RN  - 0 (tau Proteins)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Line
MH  - Cell-Free System/metabolism
MH  - Dementia/*genetics/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Microscopy, Electron
MH  - Microtubules/*metabolism/ultrastructure
MH  - *Mutation, Missense
MH  - Neuroblastoma/metabolism/pathology
MH  - Paclitaxel/pharmacology
MH  - Protein Binding/drug effects/genetics
MH  - Recombinant Proteins/genetics/metabolism
MH  - Transfection
MH  - Tubulin/metabolism
MH  - tau Proteins/*genetics/*metabolism
EDAT- 2000/01/08 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/01/08 09:00
PHST- 2000/01/08 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/01/08 09:00 [entrez]
AID - S0006-8993(99)02124-1 [pii]
AID - 10.1016/s0006-8993(99)02124-1 [doi]
PST - ppublish
SO  - Brain Res. 2000 Jan 17;853(1):5-14. doi: 10.1016/s0006-8993(99)02124-1.