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PMID: 16382152 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Modulation of prion formation, aggregation, and toxicity by the actin cytoskeleton in yeast.

Molecular and cellular biology ·Vol. 26 ·No. 2 ·2006-01-00 ·Pages 617-29

Ganusova EE, Ozolins LN, Bhagat S, Newnam GP, Wegrzyn RD, Sherman MY, Chernoff YO

Abstract

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.

MeSH Terms
Actins/metabolism Carrier Proteins/genetics,metabolism Cytoskeletal Proteins Cytoskeleton/metabolism Endocytosis Mutation Peptide Termination Factors Prions/genetics,metabolism Protein Binding Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
Actins Carrier Proteins Cytoskeletal Proteins Peptide Termination Factors Prions RNQ1 protein, S cerevisiae SLA2 protein, S cerevisiae SUP35 protein, S cerevisiae Saccharomyces cerevisiae Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ganusova Elena E
School of Biology, Georgia Institute of Technology, M/C 0230, 310 Ferst Drive, Atlanta, Georgia 30332-0230, USA.
Ozolins Laura N
Bhagat Srishti
Newnam Gary P
Wegrzyn Renee D
Sherman Michael Y
Chernoff Yury O
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.2.617-629.2006
Published
2006-01-00
Pages
617-29
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1346895
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058763 · United States
NIGMS NIH HHS · R01GM58763 · United States
External Links
PubMed source DOI: 10.1128/MCB.26.2.617-629.2006 PMC Full Text View journal details
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