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

ABSTRACT: Synucleinopathies such as Parkinson's disease are characterized by the pathological deposition of misfolded ?-synuclein aggregates into inclusions throughout the central and peripheral nervous system. Mounting evidence suggests that intercellular propagation of ?-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 ?-synuclein fibrils efficiently transfer from donor to acceptor cells through tunneling nanotubes (TNTs) inside lysosomal vesicles. Following transfer through TNTs, ?-synuclein fibrils are able to seed soluble ?-synuclein aggregation in the cytosol of acceptor cells. We propose that donor cells overloaded with ?-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.

SUBMITTER: Abounit S 

PROVIDER: S-EPMC5048354 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature