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Interaction of α‐synuclein and synphilin‐1: effect of Parkinson's disease‐associated mutations
Author(s) -
Kawamata Hibiki,
McLean Pamela J.,
Sharma Nutan,
Hyman Bradley T.
Publication year - 2001
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 - 10.1046/j.1471-4159.2001.00301.x
Subject(s) - synuclein , parkinson's disease , alpha synuclein , mutation , förster resonance energy transfer , biology , chemistry , disease , genetics , medicine , gene , pathology , fluorescence , physics , quantum mechanics
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.