Abstract
Endoplasmic reticulum (ER) stress causes the ER-resident transmembrane protein Ire1 to self-associate, leading to the formation of large oligomeric clusters. In yeast cells, this induces strong unfolded protein response (UPR) through splicing of HAC1 mRNA. Here, we demonstrate that highly ER-stressed yeast cells exhibited poor Ire1 clustering in the presence of the actin-disrupting agent latrunculin-A. Under these conditions, Ire1 may form smaller oligomers because latrunculin-A only partially diminished the Ire1-mediated splicing of HAC1 mRNA. Ire1 cluster formation was also impaired by deletion of the type-II myosin gene MYO1 or SAC6, which encodes the actin-bundling protein fimbrin. Finally, we demonstrated that Ire1 clusters are predominantly located on or near actin filaments. Therefore, we propose that actin filaments play an important role in ER stress-induced clustering of Ire1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / genetics
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Actin Cytoskeleton / metabolism
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Actins / genetics
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Actins / metabolism*
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Dithiothreitol / pharmacology
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Endoplasmic Reticulum Stress*
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Gene Deletion
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Genes, Fungal
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Microtubules / genetics
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Microtubules / metabolism
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Multigene Family
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Myosin Heavy Chains / genetics
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Myosin Heavy Chains / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA Splicing
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RNA, Fungal / genetics
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RNA, Fungal / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Thiazolidines / pharmacology
Substances
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Actins
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Basic-Leucine Zipper Transcription Factors
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Bridged Bicyclo Compounds, Heterocyclic
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HAC1 protein, S cerevisiae
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MYO1 protein, S cerevisiae
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Membrane Glycoproteins
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RNA, Fungal
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RNA, Messenger
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Thiazolidines
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IRE1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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Myosin Heavy Chains
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latrunculin A
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Dithiothreitol