1. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions.
- Author
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Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, Margolis RL, Troncoso JC, Lanahan AA, Worley PF, Dawson VL, Dawson TM, and Ross CA
- Subjects
- Amino Acid Sequence, Animals, Brain Chemistry, Carrier Proteins genetics, Cell Line, Chromosomes, Human, Pair 5 genetics, Female, Humans, Lewy Bodies metabolism, Male, Molecular Sequence Data, Nerve Tissue Proteins genetics, Parkinson Disease genetics, Parkinson Disease metabolism, Plasmids genetics, Protein Binding, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Saccharomyces cerevisiae genetics, Sequence Homology, Amino Acid, Synucleins, Tissue Distribution, Tissue Extracts metabolism, Transfection, alpha-Synuclein, Carrier Proteins metabolism, Inclusion Bodies metabolism, Nerve Tissue Proteins metabolism
- 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 alpha-synuclein). Alpha-synuclein is present in Lewy bodies of patients with sporadic PD, suggesting that alpha-synuclein may be involved in the pathogenesis of PD. It is unknown how alpha-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 alpha-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 alpha-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.
- Published
- 1999
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