Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/43218

Parkin ubiquitinates the alpha-synuclein interacting protein, synphilin-1: implications for Lewy body formation in Parkinson"s disease

Authors Chung, Kenny K.K.
Zhang, Y.
Lim, K.L.
Tanaka, Y.
Huang, H.
Gao, J.
Ross, C.
Dawson, V.L.
Dawson, T.M.
Issue Date 2001
Source Nature Med. , v. 7, (10), 2001, p. 1144-1150
Summary Parkinson disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic-ubiquitinated inclusions (Lewy bodies). Mutations in α-synuclein (A53T, A30P) and parkin cause familial Parkinson disease. Both these proteins are found in Lewy bodies. The absence of Lewy bodies in patients with parkin mutations suggests that parkin might be required for the formation of Lewy bodies. Here we show that parkin interacts with and ubiquitinates the α-synuclein-interacting protein, synphilin-1. Co-expression of α-synuclein, synphilin-1 and parkin result in the formation of Lewy-body-like ubiquitin-positive cytosolic inclusions. We further show that familial-linked mutations in parkin disrupt the ubiquitination of synphilin-1 and the formation of the ubiquitin-positive inclusions. These results provide a molecular basis for the ubiquitination of Lewy-body-associated proteins and link parkin and α-synuclein in a common pathogenic mechanism through their interaction with synphilin-1.
ISSN 1078-8956
Language English
Format Article
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