Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions

Simone Engelender, Zachary Kaminsky, Guo Xin, Alan H. Sharp, Ravi K. Amaravi, John J. Kleiderlein, Russell L. Margolis, Juan C. Troncoso, Anthony A. Lanahan, Paul F. Worley, Valina L. Dawson, Ted M. Dawson, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson disease (PD) is a neurodegenerative disease characterized by tremor, bradykinesia, rigidity and postural instability. Post-mortem examination shows loss of neurons and Lewy bodies, which are cytoplasmic eosinophilic inclusions, in the substantia nigra and other brain regions. A few families have PD caused by mutations (A53T or A30P) in the gene SNCA (encoding α-synuclein; refs 3-5). α-synuclein is present in Lewy bodies of patients with sporadic PD (refs 6,7), suggesting that α-synuclein may be involved in the pathogenesis of PD. It is unknown how α-synuclein contributes to the cellular and biochemical mechanisms of PD, and its normal functions and biochemical properties are poorly understood. To determine the protein-interaction partners of α-synuclein, we performed a yeast two- hybrid screen. We identified a novel interacting protein, which we term synphilin-1 (encoded by the gene SNCAIP). We found that α-synuclein interacts in vivo with synphilin-1 in neurons. Co-transfection of both proteins (but not control proteins) in HEK 293 cells yields cytoplasmic eosinophilic inclusions.

Original languageEnglish (US)
Pages (from-to)110-114
Number of pages5
JournalNature genetics
Volume22
Issue number1
DOIs
StatePublished - May 1999

ASJC Scopus subject areas

  • Genetics

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