Evidence map›Paper›PMID 27356871›Full record

ArticleMolecular neurodegeneration2016

Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment.

Peter Dongmin Sohn, Tara E Tracy, Hye-In Son, Yungui Zhou, Renata E P Leite, Bruce L Miller, William W Seeley, Lea T Grinberg, Li Gan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 160 citations in OpenAlex.

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  12. Modified tau leads to neuronal and global ribosome dysfunction inbioRxiv : the preprint server for biology · 2025
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38 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

9 authors at 4 institutions in 2 countries.

Peter Dongmin SohnGladstone Institute of Neurological Disease, University of California, San Francisco, CA, 94158, USA.
Tara E TracyGladstone Institute of Neurological Disease, University of California, San Francisco, CA, 94158, USA.
Hye-In SonGladstone Institute of Virology & Immunology, San Francisco, CA, 94158, USA.
Yungui ZhouGladstone Institute of Neurological Disease, University of California, San Francisco, CA, 94158, USA.
Renata E P LeitePhysiopathology in Aging Lab/Brazilian Aging Brain Study Group-LIM22, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Bruce L MillerMemory and Aging Center, Department of Neurology University of California, San Francisco, CA, 94158, USA.
William W SeeleyMemory and Aging Center, Department of Neurology University of California, San Francisco, CA, 94158, USA.
Lea T GrinbergMemory and Aging Center, Department of Neurology University of California, San Francisco, CA, 94158, USA.
Li GanGladstone Institute of Neurological Disease, University of California, San Francisco, CA, 94158, USA. lgan@gladstone.ucsf.edu.
University of California, San Francisco · USGladstone Institutes · USUniversidade de São Paulo · BRUniversity Memory and Aging Center · US

Funding

PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
Molecular mechanisms in progranulin deficient frontotemporal dementiaR01AG051390 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2015 to 2019
$2.5M
EXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1M
SIRT1 Limits Microglial Toxicity in Alzheimer's DiseaseR01AG036884 · NIA · J. DAVID GLADSTONE INSTITUTES · PI GAN, LI · 2012 to 2016
$2.0M
The Role of Cathepsin B and Cystatin C in Alzheimer's DiseaseR01AG030207 · NIA · J. DAVID GLADSTONE INSTITUTES · PI GAN, LI · 2010 to 2014
$1.9M
Pathogenic events triggered by tau acetylation in neurodegenerative tauopathyF32AG043301 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2012 to 2014
$156k
NCRR NIH HHS C06 RR018928NIA NIH HHS F32 AG043301NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG030207NIA NIH HHS R01 AG036884NIA NIH HHS R01 AG051390
6 · The paper itself

Abstract

backgroundNeurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood.

resultsHere we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and βIV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures.

conclusionsTogether, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS.

Indexed as

Cell PolarityAcetylationAgedAged, 80 and overAlzheimer DiseaseAnimalsAxon Initial SegmentBlotting, WesternCytoskeletonDisease Models, AnimalFemaleHumansImmunohistochemistryMaleMiceMice, Inbred C57BLtau ProteinsAlzheimer’s diseaseAxon initial segmentNeuronal cytoskeletonNeuronal polarityTau acetylation

Identifiers

PMID27356871
PMCPMC4928318
OpenAlexW2466670739

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Registered trials

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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.