Interaction of α-synuclein and synphilin-1: Effect of Parkinson's disease-associated mutations

Hibiki Kawamata, Pamela J McLean, Nutan Sharma, Bradley T. Hyman

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

α-Synuclein is a major component of Lewy bodies, a neuropathological feature of Parkinson's disease. Two α-synuclein mutations, Ala53Thr and Ala30Pro, are associated with early onset, familial forms of the disease. Recently, synphilin-1, a protein found to interact with α-synuclein by yeast two hybrid techniques, was detected in Lewy bodies. In this study we report the interaction of α-synuclein and synphilin-1 in human neuroglioma cells using a sensitive fluorescence resonance energy transfer technique. We demonstrate that the C-terminus of α-synuclein is closely associated with the C-terminus of synphilin-1. A weak interaction occurs between the N-terminus of α-synuclein and synphilin-1. The familial Parkinson's disease associated mutations of α-synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between their C-terminal regions and synphilin-1. However, compared with wild-type α-synuclein, significantly less energy transfer occurs between the C-terminus of Ala53Thr α-synuclein and synphilin-1, suggesting that the Ala53Thr mutation alters the conformation of α-synuclein in relation to synphilin-1.

Original languageEnglish (US)
Pages (from-to)929-934
Number of pages6
JournalJournal of Neurochemistry
Volume77
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Synucleins
Parkinson Disease
Mutation
Lewy Bodies
Fluorescence Resonance Energy Transfer
Energy Transfer
Yeast
Energy transfer
Conformations

Keywords

  • α-synuclein
  • FRET
  • Human neuroglioma cells
  • Parkinson's disease
  • Synphilin-1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Interaction of α-synuclein and synphilin-1 : Effect of Parkinson's disease-associated mutations. / Kawamata, Hibiki; McLean, Pamela J; Sharma, Nutan; Hyman, Bradley T.

In: Journal of Neurochemistry, Vol. 77, No. 3, 2001, p. 929-934.

Research output: Contribution to journalArticle

Kawamata, Hibiki ; McLean, Pamela J ; Sharma, Nutan ; Hyman, Bradley T. / Interaction of α-synuclein and synphilin-1 : Effect of Parkinson's disease-associated mutations. In: Journal of Neurochemistry. 2001 ; Vol. 77, No. 3. pp. 929-934.
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