This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maselli, A.
Right arrow Articles by Fechheimer, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maselli, A.
Right arrow Articles by Fechheimer, M.

 Previous Article  |  Next Article 

Eukaryotic Cell, August 2003, p. 778-787, Vol. 2, No. 4
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.4.778-787.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

Andrew Maselli, Ruth Furukawa, Susanne A. M. Thomson, Richard C. Davis, and Marcus Fechheimer*

Department of Cellular Biology, University of Georgia, Athens, Georgia 30602

Received 12 November 2002/ Accepted 22 April 2003

Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa {Delta}EF1. The 34-kDa {Delta}EF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa {Delta}EF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa {Delta}EF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and {alpha}-actinin. Finally, the expression of the 34-kDa {Delta}EF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton.

* Corresponding author. Mailing address: Department of Cellular Biology, 724 Biological Sciences Building, University of Georgia, Athens, GA 30602. Phone: (706) 542-3338. Fax: (706) 542-4271. E-mail: fechheim{at}cb.uga.edu.

Eukaryotic Cell, August 2003, p. 778-787, Vol. 2, No. 4
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.4.778-787.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Reyes, J. F., Stone, K., Ramos, J., Maselli, A. (2009). Formation of Hirano Bodies after Inducible Expression of a Modified Form of an Actin-Cross-Linking Protein. Eukaryot Cell 8: 852-857 [Abstract] [Full Text]  
  • Lazaro-Dieguez, F., Aguado, C., Mato, E., Sanchez-Ruiz, Y., Esteban, I., Alberch, J., Knecht, E., Egea, G. (2008). Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide. J. Cell Sci. 121: 1415-1425 [Abstract] [Full Text]  
  • Jang, D.-H., Han, J.-H., Lee, S.-H., Lee, Y.-S., Park, H., Lee, S.-H., Kim, H., Kaang, B.-K. (2005). Cofilin expression induces cofilin-actin rod formation and disrupts synaptic structure and function in Aplysia synapses. Proc. Natl. Acad. Sci. USA 102: 16072-16077 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»