Oligomeric alpha-synuclein inhibits tubulin polymerization.
Earlier investigations have demonstrated that tubulin co-localizes with alpha-synuclein in Lewy bodies and influences the formation of alpha-synuclein aggregation. However, it is not clear whether aggregated alpha-synuclein has any effects on the function of tubulin, i.e. tubulin polymerization, a critical mechanism by which neurons maintain their morphology and execute functions. In this study, we evaluated the effects of aggregated alpha-synuclein on tubulin polymerization in dopaminergic neurons (MES cells), along with mitochondrial function, cell morphology, and viability. The results indicate that MES cells exposed to extracellular oligomeric alpha-synuclein exhibited decreased tubulin polymerization and mitochondrial function as well as morphological alternation long before cell death. Further investigation showed that internalization of oligomeric alpha-synuclein by neurons appeared to be critical in the process, although direct interaction between tubulin and intracellular oligomeric alpha-synuclein was not necessary. Finally, we demonstrated that neurotoxicity induced by oligomeric alpha-synuclein was largely prevented by overexpressing the neuroprotective protein, DJ-1.
Chen
Leo
L
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Jin
Jinghua
J
Davis
Jeanne
J
Zhou
Yong
Y
Wang
Yan
Y
Liu
Jun
J
Lockhart
Paul J
PJ
Zhang
Jing
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006822:Hybrid Cells; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008636:Mesencephalon; D008928:Mitochondria / Q000502:physiology; D015513:Oncogene Proteins / Q000502:physiology; D011108:Polymers / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014404:Tubulin / Q000502:physiology*; D051844:alpha-Synuclein / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011108:Polymers; D011954:Receptors, Dopamine; D014404:Tubulin; D051844:alpha-Synuclein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1