Secretion of Tau via an Unconventional Non-vesicular Mechanism

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Merezhko , M , Brunello , C A , Yan , X , Vihinen , H , Jokitalo , E , Uronen , R-L & Huttunen , H J 2018 , ' Secretion of Tau via an Unconventional Non-vesicular Mechanism ' , Cell Reports , vol. 25 , no. 8 , pp. 2027-+ .

Title: Secretion of Tau via an Unconventional Non-vesicular Mechanism
Author: Merezhko, Maria; Brunello, Cecilia A.; Yan, Xu; Vihinen, Helena; Jokitalo, Eija; Uronen, Riikka-Liisa; Huttunen, Henri J.
Contributor organization: Neuroscience Center
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Institute of Biotechnology
Electron Microscopy
Henri Juhani Huttunen / Principal Investigator
Date: 2018-11-20
Language: eng
Number of pages: 13
Belongs to series: Cell Reports
ISSN: 2211-1247
Abstract: Tauopathies are characterized by cerebral accumulation of Tau protein aggregates that appear to spread throughout the brain via a cell-to-cell transmission process that includes secretion and uptake of pathological Tau, followed by templated misfolding of normal Tau in recipient cells. Here, we show that phosphorylated, oligomeric Tau clusters at the plasma membrane in N2A cells and is secreted in vesicle-free form in an unconventional process sensitive to changes in membrane properties, particularly cholesterol and sphingomyelin content. Cell surface heparan sulfate proteoglycans support Tau secretion, possibly by facilitating its release after membrane penetration. Notably, secretion of endogenous Tau from primary cortical neurons is mediated, at least partially, by a similar mechanism. We suggest that Tau is released from cells by an unconventional secretory mechanism that involves its phosphorylation and oligomerization and that membrane interaction may help Tau to acquire properties that allow its escape from cells directly through the plasma membrane.
3112 Neurosciences
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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