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Non‐classical exocytosis of α‐synuclein is sensitive to folding states and promoted under stress conditions
Author(s) -
Jang Ara,
Lee HeJin,
Suk JiEun,
Jung JinWoo,
Kim KwangPyo,
Lee SeungJae
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06695.x
Subject(s) - exocytosis , endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , vesicle , secretion , protein folding , golgi apparatus , chemistry , munc 18 , synuclein , neuroinflammation , synaptic vesicle , protein aggregation , secretory pathway , alpha synuclein , cytosol , biology , biochemistry , parkinson's disease , medicine , inflammation , disease , immunology , enzyme , membrane
J. Neurochem. (2010) 113 , 1263–1274. Abstract 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.