Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions
Autor: | Christopher A. Ross, Zachary Kaminsky, Ted M. Dawson, John J. Kleiderlein, Paul F. Worley, Valina L. Dawson, Alan H. Sharp, Simone Engelender, Anthony Lanahan, Xin Guo, Juan C. Troncoso, Russell L. Margolis, Ravi K. Amaravi |
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Rok vydání: | 1999 |
Předmět: |
Male
Molecular Sequence Data Synucleins Nerve Tissue Proteins Substantia nigra Saccharomyces cerevisiae Plasma protein binding Biology Transfection Cell Line chemistry.chemical_compound Gene expression Genetics Animals Humans Tissue Distribution Amino Acid Sequence RNA Messenger Brain Chemistry Inclusion Bodies Alpha-synuclein Sequence Homology Amino Acid Tissue Extracts HEK 293 cells Synphilin-1 Parkinson Disease Rats nervous system diseases Cell biology nervous system chemistry Cytoplasm alpha-Synuclein Chromosomes Human Pair 5 Female Lewy Bodies Carrier Proteins Plasmids Protein Binding |
Zdroj: | Nature Genetics. 22:110-114 |
ISSN: | 1546-1718 1061-4036 |
Popis: | 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. |
Databáze: | OpenAIRE |
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