Evidence map›Paper›PMID 15020716›Full record

ArticleMolecular biology of the cell2004

Modulation of microtubule dynamics by tau in living cells: implications for development and neurodegeneration.

Janis M Bunker, Leslie Wilson, Mary Ann Jordan, Stuart C Feinstein

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 150 citations in OpenAlex.

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  18. Developmental Pathogenicity of 4-Repeat Human Tau Is Lost with the P301L Mutation in Genetically Matched Tau-Transgenic Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Janis M BunkerNeuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
Leslie Wilson
Mary Ann Jordan
Stuart C Feinstein
University of California, Santa Barbara · US

Funding

Mechanism &Control of Brain Microtubule DynamicsR01NS013560 · NINDS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI WILSON, LESLIE · 1985 to 2009
$2.9M
The Molecular Structure and Function of Tau ProteinR01NS035010 · NINDS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI FEINSTEIN, STUART C · 1996 to 2010
$2.7M
Mechanisms of Action of Anti-Mitotic DrugsR01CA057291 · NCI · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI JORDAN, MARY ANN · 1992 to 2007
$2.2M
NCI NIH HHS CA57291NCI NIH HHS R01 CA057291NINDS NIH HHS NS13560NINDS NIH HHS NS35010NINDS NIH HHS R01 NS013560NINDS NIH HHS R01 NS035010
6 · The paper itself

Abstract

The neural microtubule-associated protein tau binds to and stabilizes microtubules. Because of alternative mRNA splicing, tau is expressed with either 3 or 4 C-terminal repeats. Two observations indicate that differences between these tau isoforms are functionally important. First, the pattern of tau isoform expression is tightly regulated during development. Second, mutation-induced changes in tau RNA splicing cause neuronal cell death and dementia simply by altering the isoform expression ratio. To investigate whether 3- and 4-repeat tau differentially regulate microtubule behavior in cells, we microinjected physiological levels of these two isoforms into EGFP-tubulin-expressing cultured MCF7 cells and measured the effects on the dynamic instability behavior of individual microtubules by time-lapse microscopy. Both isoforms suppressed microtubule dynamics, though to different extents. Specifically, 4-repeat tau reduced the rate and extent of both growing and shortening events. In contrast, 3-repeat tau stabilized most dynamic parameters about threefold less potently than 4-repeat tau and had only a minimal ability to suppress shortening events. These differences provide a mechanistic rationale for the developmental shift in tau isoform expression and are consistent with a loss-of-function model in which abnormal tau isoform expression results in the inability to properly regulate microtubule dynamics, leading to neuronal cell death and dementia.

Indexed as

Cell Line, TumorHumansMicroinjectionsMicroscopy, FluorescenceMicrotubulesNeurodegenerative DiseasesProtein IsoformsRepetitive Sequences, Amino Acidtau ProteinsTime FactorsProtein Isoformstau Proteins

Identifiers

PMID15020716
PMCPMC420096
OpenAlexW2165300068

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.