Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes.
EMBO J
; 35(19): 2120-2138, 2016 10 04.
Article
em En
| MEDLINE
| ID: mdl-27550960
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comunicação Celular
/
Nanotubos
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Alfa-Sinucleína
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Amiloide
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Lisossomos
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França