Reference - Detail
RRC ID | 12153 |
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Author | Iwata A, Miura S, Kanazawa I, Sawada M, Nukina N. |
Title | alpha-Synuclein forms a complex with transcription factor Elk-1. |
Journal | J Neurochem |
Abstract |
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. |
Volume | 77(1) |
Pages | 239-52 |
Published | 2001-4-1 |
DOI | 10.1046/j.1471-4159.2001.t01-1-00232.x |
PMID | 11279280 |
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 |
IF | 4.066 |
Times Cited | 88 |
WOS Category | NEUROSCIENCES BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
DNA material | pZRmERK2 (RDB01796) |