Abstract:
:α-Synuclein causes Parkinson's disease if mutated or aberrantly produced in neurons. α-Synuclein-lipid interactions are important for the normal function of the protein, but can also contribute to pathogenesis. We previously reported that deletion of the first 10 N-terminal amino acids dramatically reduced lipid binding in vitro, as well as membrane binding and toxicity in yeast. Here we extend this study to human neuroblastoma SHSY-5Y cells, and find that in these cells the first 10 N-terminal residues do not affect α-synuclein membrane binding, self-association and cell viability, contrary to yeast. Differences in lipid composition, membrane fluidity and cytosolic factors between yeast and neuronal cells may account for the distinct binding behavior of the truncated variant in these two systems. Retinoic acid promotes differentiation and α-synuclein oligomer formation in neuroblastoma cells, while addition of a proteasomal inhibitor induces neurite outgrowth and toxicity to certain wild-type and truncated α-synuclein clones. Yeast recapitulate several features of α-synuclein (patho)biology, but its simplicity sets limitations; verification of yeast results in more relevant model systems is, therefore, essential.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Vamvaca K,Lansbury PT Jr,Stefanis Ldoi
10.1111/j.1471-4159.2011.07431.xsubject
Has Abstractpub_date
2011-10-01 00:00:00pages
389-97issue
2eissn
0022-3042issn
1471-4159journal_volume
119pub_type
杂志文章abstract::The glutamate receptor 2 (GluR2) subunit determines many of the functional properties of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate subtype of glutamate receptor. The roles of untranslated regions (UTRs) in mRNA stability, transport, or translation are increasingly recognized. The 3' end of the GluR2 tra...
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
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更新日期:2000-12-01 00:00:00
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2007-12-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2004-05-01 00:00:00