Parkin ubiquitinates the α-synuclein–interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease

Content Provider	Semantic Scholar
Author	Chung, Kenny K. K. Zhang, Yi Lim, Kah Leong Tanaka, Yuji Huang, Hui Ross, Christopher A. Dawson, Valina L. Dawson, Ted M.
Copyright Year	2001
Abstract	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.
Starting Page	1144
Ending Page	1150
Page Count	7
File Format	PDF HTM / HTML
DOI	10.1038/nm1001-1144
Alternate Webpage(s)	http://neuroscience.jhu.edu/files2/publications_Ross_C_ross1144-1150.pdf
PubMed reference number	11590439
Alternate Webpage(s)	https://doi.org/10.1038/nm1001-1144
Journal	Medline
Volume Number	7
Journal	Nature Medicine
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article