TY - JOUR
T1 - Interaction of α-synuclein and synphilin-1
T2 - Effect of Parkinson's disease-associated mutations
AU - Kawamata, Hibiki
AU - McLean, Pamela J.
AU - Sharma, Nutan
AU - Hyman, Bradley T.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - FRET
KW - Human neuroglioma cells
KW - Parkinson's disease
KW - Synphilin-1
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=0034996655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034996655&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2001.00301.x
DO - 10.1046/j.1471-4159.2001.00301.x
M3 - Article
C2 - 11331421
AN - SCOPUS:0034996655
SN - 0022-3042
VL - 77
SP - 929
EP - 934
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 3
ER -