Reference - Detail
|Author||Iwata A, Miura S, Kanazawa I, Sawada M, Nukina N.|
|Title||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||Amino Acid Motifs / genetics Animals Binding Sites Cell Line Cytoplasmic Granules / metabolism DNA-Binding Proteins* Humans Lewy Body Disease / metabolism MAP Kinase Signaling System / drug effects Macromolecular Substances Mice Mitogen-Activated Protein Kinase 1 / metabolism Multiple System Atrophy / metabolism Mutagenesis, Site-Directed Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Nerve Tissue Proteins / pharmacology Neuroglia / cytology Neuroglia / metabolism Neurons / cytology Neurons / metabolism Parkinson Disease / genetics Parkinson Disease / metabolism Phosphorylation / drug effects Precipitin Tests Protein Binding / genetics Protein Structure, Tertiary Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Synucleins Transcription Factors / genetics Transcription Factors / metabolism* Transfection alpha-Synuclein ets-Domain Protein Elk-1|
|WOS Category||NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY|
|DNA material||pZRmERK2 (RDB01796)|