Membrane interaction and disulphide-bridge formation in the unconventional secretion of Tau

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Hellen , M , Bhattacharjee , A , Uronen , R-L & Huttunen , H J 2021 , ' Membrane interaction and disulphide-bridge formation in the unconventional secretion of Tau ' , Bioscience Reports , vol. 41 , no. 8 , 20210148 . https://doi.org/10.1042/BSR20210148

Title: Membrane interaction and disulphide-bridge formation in the unconventional secretion of Tau
Author: Hellen, Marianna; Bhattacharjee, Arnab; Uronen, Riikka-Liisa; Huttunen, Henri J.
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Biosciences
Date: 2021-08
Language: eng
Number of pages: 10
Belongs to series: Bioscience Reports
ISSN: 0144-8463
URI: http://hdl.handle.net/10138/336426
Abstract: Misfolded, pathological tau protein propagates from cell to cell causing neuronal degeneration in Alzheimer's disease and other tauopathies. The molecular mechanisms of this process have remained elusive. Unconventional secretion of tau takes place via several different routes, including direct penetration through the plasma membrane. Here, we show that tau secretion requires membrane interaction via disulphide bridge formation. Mutating residues that reduce tau interaction with membranes or formation of disulphide bridges decrease both tau secretion from cells, and penetration through artificial lipid membranes. Our results demonstrate that tau is indeed able to penetrate protein-free membranes in a process independent of active cellular processes and that both membrane interaction and disulphide bridge formation are needed for this process. QUARK-based de novo modelling of the second and third microtubule-binding repeat domains (MTBDs), in which the two cysteine residues of 4R isoforms of tau are located, supports the concept that this region of tau could form transient amphipathic helices for membrane interaction.
Subject: FIBROBLAST-GROWTH-FACTOR
3-DIMENSIONAL STRUCTURE
PROTEIN
PROPAGATION
3112 Neurosciences
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