Using leucine zipper to facilitate α-synuclein assembly

Peizhou Jiang, Li Wen Ko, Karen R. Jansen, Todd E. Golde, Shu Hui Yen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The accumulation of filamentous α-synuclein (α-S) is associated with Parkinson's disease. It remains controversial as to the mode (antiparallel or parallel) of α-S self-assembly and whether an exact alignment of the central hydrophobic region is essential. In the present study, we performed in vitro assembly using α-S with or without the attachment of artificial leucine zippers (Zips) capable of forming either parallel or antiparallel coiled coils and included a spacer in one derivative. Results showed that Zips accelerate filament assembly in both the parallel and antiparallel fashions, that a precise alignment of the central hydrophobic region is not essential, and that the antiparallel pairs displayed the highest thioflavin T signals. More importantly, cells expressing Zip-fused α-S, but not α-S alone, formed α-S immunopositive and thioflavin S-positive inclusions in 7 days. The results suggest that α-S can assemble in both parallel and antiparallel modes but have a higher tendency to assemble in the latter mode and that cells overexpressing Zip-fused α-S may be used to screen α-S assembly inhibitors due to enhanced ability to form inclusions.

Original languageEnglish (US)
Pages (from-to)3165-3174
Number of pages10
JournalFASEB Journal
Volume22
Issue number9
DOIs
StatePublished - Sep 2008

Fingerprint

Synucleins
Leucine Zippers
leucine zipper
Parkinson disease
Parkinson Disease
Fasteners
cells
Self assembly
Cells
Derivatives
thioflavin T

Keywords

  • Adeno-associated virus
  • Aggregation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Jiang, P., Ko, L. W., Jansen, K. R., Golde, T. E., & Yen, S. H. (2008). Using leucine zipper to facilitate α-synuclein assembly. FASEB Journal, 22(9), 3165-3174. https://doi.org/10.1096/fj.08-108365

Using leucine zipper to facilitate α-synuclein assembly. / Jiang, Peizhou; Ko, Li Wen; Jansen, Karen R.; Golde, Todd E.; Yen, Shu Hui.

In: FASEB Journal, Vol. 22, No. 9, 09.2008, p. 3165-3174.

Research output: Contribution to journalArticle

Jiang, P, Ko, LW, Jansen, KR, Golde, TE & Yen, SH 2008, 'Using leucine zipper to facilitate α-synuclein assembly', FASEB Journal, vol. 22, no. 9, pp. 3165-3174. https://doi.org/10.1096/fj.08-108365
Jiang, Peizhou ; Ko, Li Wen ; Jansen, Karen R. ; Golde, Todd E. ; Yen, Shu Hui. / Using leucine zipper to facilitate α-synuclein assembly. In: FASEB Journal. 2008 ; Vol. 22, No. 9. pp. 3165-3174.
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