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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

Authors: Francesc X. Guix, Ragna Sannerud, Fedor Berditchevski, Amaia M. Arranz, Katrien Horré, An Snellinx, Amantha Thathiah, Takaomi Saido, Takashi Saito, Sundaresan Rajesh, Michael Overduin, Samir Kumar-Singh, Enrico Radaelli, Nikky Corthout, Julien Colombelli, Sébastien Tosi, Sebastian Munck, Isabel H. Salas, Wim Annaert, Bart De Strooper

Published in: Molecular Neurodegeneration | Issue 1/2017

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Abstract

Background

The mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer’s disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase.

Methods

We searched for tetraspanins with altered expression in AD brains. The function of the selected tetraspanin was studied in vitro and the physiological relevance of our findings was confirmed in vivo.

Results

Tetraspanin-6 (TSPAN6) is increased in AD brains and overexpression in cells exerts paradoxical effects on Amyloid Precursor Protein (APP) metabolism, increasing APP-C-terminal fragments (APP-CTF) and Aβ levels at the same time. TSPAN6 affects autophagosome-lysosomal fusion slowing down the degradation of APP-CTF. TSPAN6 recruits also the cytosolic, exosome-forming adaptor syntenin which increases secretion of exosomes that contain APP-CTF.

Conclusions

TSPAN6 is a key player in the bifurcation between lysosomal-dependent degradation and exosome mediated secretion of APP-CTF. This corroborates the central role of the autophagosomal/lysosomal pathway in APP metabolism and shows that TSPAN6 is a crucial player in APP-CTF turnover.
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Metadata
Title
Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments
Authors
Francesc X. Guix
Ragna Sannerud
Fedor Berditchevski
Amaia M. Arranz
Katrien Horré
An Snellinx
Amantha Thathiah
Takaomi Saido
Takashi Saito
Sundaresan Rajesh
Michael Overduin
Samir Kumar-Singh
Enrico Radaelli
Nikky Corthout
Julien Colombelli
Sébastien Tosi
Sebastian Munck
Isabel H. Salas
Wim Annaert
Bart De Strooper
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0165-0

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