alpha-Synuclein forms a complex with transcription factor Elk-1.
alpha-Synuclein has been identified as a component of Lewy bodies in Parkinson's disease and diffuse Lewy body disease, and glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). To explore the role of alpha-synuclein in the pathogenesis, we searched for molecules interacting with alpha-synuclein and discovered that GCIs are stained ... by anti-Elk-1 antibody. To seek the role of Elk-1 in synucleinopathies, we cotransfected alpha-synuclein and Elk-1 to cultured cells, and found small granular structure complexes where the two molecules colocalized. Moreover, alpha-synuclein and Elk-1 were co-immunoprecipitated from the cell lysates. For formation of the complex, the presence of both ETS and B-box domains of Elk-1 was required. Although there was no evidence of direct binding between alpha-synuclein and Elk-1, we discovered that alpha-synuclein and Elk-1 both bind to ERK-2, a MAP kinase. The effect of alpha-synuclein on the MAP kinase pathway was assessed using the Pathdetect system, which showed prominent attenuation of Elk-1 phosphorylation with alpha-synuclein, and especially A53T mutant. Our results suggest that alpha-synuclein reacts with the MAP kinase pathway, which might cause dysfunction of neurons and oligodendrocytes and lead to neurodegeneration in Parkinson's disease and MSA.
Mesh Terms:
Amino Acid Motifs, Animals, Binding Sites, Cell Line, Cytoplasmic Granules, DNA-Binding Proteins, Humans, Lewy Body Disease, MAP Kinase Signaling System, Macromolecular Substances, Mice, Mitogen-Activated Protein Kinase 1, Multiple System Atrophy, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Neuroglia, Neurons, Parkinson Disease, Phosphorylation, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Synucleins, Transcription Factors, Transfection, alpha-Synuclein, ets-Domain Protein Elk-1
Amino Acid Motifs, Animals, Binding Sites, Cell Line, Cytoplasmic Granules, DNA-Binding Proteins, Humans, Lewy Body Disease, MAP Kinase Signaling System, Macromolecular Substances, Mice, Mitogen-Activated Protein Kinase 1, Multiple System Atrophy, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Neuroglia, Neurons, Parkinson Disease, Phosphorylation, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Synucleins, Transcription Factors, Transfection, alpha-Synuclein, ets-Domain Protein Elk-1
J. Neurochem.
Date: Apr. 01, 2001
PubMed ID: 11279280
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