Non-classical exocytosis of alpha-synuclein is sensitive to folding states and promoted under stress conditions.
J Neurochem
; 113(5): 1263-74, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20345754
ABSTRACT
Parkinson's disease is characterized by deposition of misfolded/aggregated alpha-synuclein proteins in multiple regions of the brain. Neurons can release alpha-synuclein; through this release, pathological forms of alpha-synuclein are propagated between neurons, and also cause neuroinflammation. In this study, we demonstrate that release of alpha-synuclein is consistently increased under various protein misfolding stress conditions in both neuroblastoma and primary neuron models. This release is mediated by a non-classical, endoplasmic reticulum (ER)/Golgi-independent exocytosis, and stress-induced release coincides with increased translocation of alpha-synuclein into vesicles. Both vesicle translocation and secretion were blocked by attachment of a highly stable, globular protein to alpha-synuclein, whereas forced protein misfolding resulted in an increase in both of these activities. Mass spectrometry analysis showed a higher degree of oxidative modification in secreted alpha-synuclein than in the cellular protein. Together, these results suggest that structurally abnormal, damaged alpha-synuclein proteins translocate preferentially into vesicles and are released from neuronal cells via exocytosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Dobramento de Proteína
/
Alfa-Sinucleína
/
Exocitose
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2010
Tipo de documento:
Article