These authors equally contributed to this work.
Non-classical exocytosis of α-synuclein is sensitive to folding states and promoted under stress conditions
Article first published online: 24 MAR 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 113, Issue 5, pages 1263–1274, June 2010
How to Cite
Jang, A., Lee, H.-J., Suk, J.-E., Jung, J.-W., Kim, K.-P. and Lee, S.-J. (2010), Non-classical exocytosis of α-synuclein is sensitive to folding states and promoted under stress conditions. Journal of Neurochemistry, 113: 1263–1274. doi: 10.1111/j.1471-4159.2010.06695.x
- Issue published online: 4 MAY 2010
- Article first published online: 24 MAR 2010
- Received December 9, 2009; revised manuscript received March 12, 2010; accepted March 15, 2010.
- neurodegenerative disease;
- Parkinson’s disease;
- protein aggregation;
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.