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Article

Nuclear Localization of α-Synuclein and Its Interaction with Histones^†

John Goers,^‡^§ Amy B. Manning-Bog, Alison L. McCormack, Ian S. Millett,^# Sebastian Doniach,^# Donato A. Di Monte, Vladimir N. Uversky,*^‡ and Anthony L. Fink*^‡

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, Department of Chemistry and Biochemistry, California Polytechnic State University, San Luis Obispo, The Parkinson's Institute, Sunnyvale, California 94089, and Departments of Chemistry and Physics, Stanford University, Stanford, California 94305

Biochemistry, 2003, 42 (28), pp 8465–8471

DOI: 10.1021/bi0341152

Publication Date (Web): June 24, 2003

†

This work was supported by grants (NS39985, NS40132, and ES10806) from the National Institutes of Health.

‡

University of California.

California Polytechnic State University.

The Parkinson's Institute.

Stanford University.

To whom correspondence should be addressed: Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064. Tel: 831-459-2744. Fax: 831-459-2935. E-mail: enzyme@cats.ucsc.edu.

Abstract

The aggregation of α-synuclein is believed to play an important role in the pathogenesis of Parkinson's disease as well as other neurodegenerative disorders (“synucleinopathies”). However, the function of α-synuclein under physiologic and pathological conditions is unknown, and the mechanism of α-synuclein aggregation is not well understood. Here we show that α-synuclein forms a tight 2:1 complex with histones and that the fibrillation rate of α-synuclein is dramatically accelerated in the presence of histones in vitro. We also describe the presence of α-synuclein and its co-localization with histones in the nuclei of nigral neurons from mice exposed to a toxic insult (i.e., injections of the herbicide paraquat). These observations indicate that translocation into the nucleus and binding with histones represent potential mechanisms underlying α-synuclein pathophysiology.

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