MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 Ganusova, E. E.
Right arrow Articles by Chernoff, Y. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ganusova, E. E.
Right arrow Articles by Chernoff, Y. O.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2006, p. 617-629, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.617-629.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Modulation of Prion Formation, Aggregation, and Toxicity by the Actin Cytoskeleton in Yeast

Elena E. Ganusova,1,{dagger} Laura N. Ozolins,1,{ddagger} Srishti Bhagat,1 Gary P. Newnam,1 Renee D. Wegrzyn,1,§ Michael Y. Sherman,2 and Yury O. Chernoff1*

School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, M/C 0230, 310 Ferst Drive, Atlanta, Georgia 30332-0230,1 Department of Biochemistry, Boston University School of Medicine, K323, 715 Albany St., Boston, Massachusetts 021182

Received 3 June 2005/ Returned for modification 22 July 2005/ Accepted 31 October 2005

Self-perpetuating protein aggregates transmit prion diseases in mammals and heritable traits in yeast. De novo prion formation can be induced by transient overproduction of the corresponding prion-forming protein or its prion domain. Here, we demonstrate that the yeast prion protein Sup35 interacts with various proteins of the actin cortical cytoskeleton that are involved in endocytosis. Sup35-derived aggregates, generated in the process of prion induction, are associated with the components of the endocytic/vacuolar pathway. Mutational alterations of the cortical actin cytoskeleton decrease aggregation of overproduced Sup35 and de novo prion induction and increase prion-related toxicity in yeast. Deletion of the gene coding for the actin assembly protein Sla2 is lethal in cells containing the prion isoforms of both Sup35 and Rnq1 proteins simultaneously. Our data are consistent with a model in which cytoskeletal structures provide a scaffold for generation of large aggregates, resembling mammalian aggresomes. These aggregates promote prion formation. Moreover, it appears that the actin cytoskeleton also plays a certain role in counteracting the toxicity of the overproduced potentially aggregating proteins.

* Corresponding author. Mailing address: School of Biology, Georgia Institute of Technology, M/C 0230, 310 Ferst Drive, Atlanta, GA 30332-0230. Phone: (404) 894-1157. Fax: (404) 894-0519. E-mail: yury.chernoff{at}biology.gatech.edu.

{dagger} Present address: Institute of Biophysics, Krasnoyarsk 660036, Russia.

{ddagger} Present address: University of Toronto School of Medicine, Toronto, Ontario, Canada.

§ Present address: Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany.

Molecular and Cellular Biology, January 2006, p. 617-629, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.617-629.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2006 by the American Society for Microbiology. All rights reserved.