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@ARTICLE{Katsinelos:136033,
author = {T. Katsinelos$^*$ and M. Zeitler and E. Dimou and A.
Karakatsani and H.-M. Müller and E. Nachman$^*$ and J. P.
Steringer and C. Ruiz de Almodovar and W. Nickel and T.
Jahn$^*$},
title = {{U}nconventional {S}ecretion {M}ediates the
{T}rans-cellular {S}preading of {T}au.},
journal = {Cell reports},
volume = {23},
number = {7},
issn = {2211-1247},
address = {Maryland Heights, MO},
publisher = {Cell Press},
reportid = {DKFZ-2018-00732},
pages = {2039 - 2055},
year = {2018},
note = {DKFZ-ZMBH-Allianz},
abstract = {The progressive deposition of misfolded hyperphosphorylated
tau is a pathological hallmark of tauopathies, including
Alzheimer's disease. However, the underlying molecular
mechanisms governing the intercellular spreading of tau
species remain elusive. Here, we show that full-length
soluble tau is unconventionally secreted by direct
translocation across the plasma membrane. Increased
secretion is favored by tau hyperphosphorylation, which
provokes microtubule detachment and increases the
availability of free protein inside cells. Using a series of
binding assays, we show that free tau interacts with
components enriched at the inner leaflet of the plasma
membrane, finally leading to its translocation across the
plasma membrane mediated by sulfated proteoglycans. We
provide further evidence that secreted soluble tau species
spread trans-cellularly and are sufficient for the induction
of intracellular tau aggregation in adjacent cells. Our
study demonstrates the mechanistic details of tau secretion
and provides insights into the initiation and progression of
tau pathology.},
cin = {B180},
ddc = {570},
cid = {I:(DE-He78)B180-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29768203},
doi = {10.1016/j.celrep.2018.04.056},
url = {https://inrepo02.dkfz.de/record/136033},
}