We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Non-classical exocytosis of α-synuclein is sensitive to folding states and promoted under stress conditions.
- Authors
Ara Jang; He-Jin Lee; Ji-Eun Suk; Jin-Woo Jung; Kwang-Pyo Kim; Seung-Jae Lee
- Abstract
J. Neurochem. (2010) 113, 1263–1274. Parkinson’s disease is characterized by deposition of misfolded/aggregated α-synuclein proteins in multiple regions of the brain. Neurons can release α-synuclein; through this release, pathological forms of α-synuclein are propagated between neurons, and also cause neuroinflammation. In this study, we demonstrate that release of α-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 α-synuclein into vesicles. Both vesicle translocation and secretion were blocked by attachment of a highly stable, globular protein to α-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 α-synuclein than in the cellular protein. Together, these results suggest that structurally abnormal, damaged α-synuclein proteins translocate preferentially into vesicles and are released from neuronal cells via exocytosis.
- Subjects
EXOCYTOSIS; NERVOUS system; NEUROBLASTOMA; SPECTROMETRY; PARKINSON'S disease
- Publication
Journal of Neurochemistry, 2010, Vol 113, Issue 5, p1263
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2010.06695.x