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EMBO J. 2016 Oct 4;35(19):2120-2138. Epub 2016 Aug 22.

Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes.

Author information

1
Institut Pasteur, Unité Trafic Membranaire et Pathogénèse, Paris Cedex 15, France.
2
Paris-Saclay Institute of Neuroscience, CNRS, Gif-sur-Yvette, France.
3
Laboratoire d'Analyse d'Images Quantitative, Institut Pasteur, Paris Cedex 15, France.
4
Institut Pasteur, Unité Trafic Membranaire et Pathogénèse, Paris Cedex 15, France chiara.zurzolo@pasteur.fr.

Abstract

Synucleinopathies such as Parkinson's disease are characterized by the pathological deposition of misfolded α-synuclein aggregates into inclusions throughout the central and peripheral nervous system. Mounting evidence suggests that intercellular propagation of α-synuclein aggregates may contribute to the neuropathology; however, the mechanism by which spread occurs is not fully understood. By using quantitative fluorescence microscopy with co-cultured neurons, here we show that α-synuclein fibrils efficiently transfer from donor to acceptor cells through tunneling nanotubes (TNTs) inside lysosomal vesicles. Following transfer through TNTs, α-synuclein fibrils are able to seed soluble α-synuclein aggregation in the cytosol of acceptor cells. We propose that donor cells overloaded with α-synuclein aggregates in lysosomes dispose of this material by hijacking TNT-mediated intercellular trafficking. Our findings thus reveal a possible novel role of TNTs and lysosomes in the progression of synucleinopathies.

KEYWORDS:

TNTs; intercellular transfer; synucleinopathies; α‐synuclein

PMID:
27550960
PMCID:
PMC5048354
DOI:
10.15252/embj.201593411
[Indexed for MEDLINE]
Free PMC Article

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