title: F-actin and a type-II myosin are required for efficient clustering of the ER stress sensor Ire1.
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.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan. kimata@bs.naist.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishiwata-Kimata
authors.forename: Yo-Hei
authors.initials: YH
authors.lastname: Yamamoto
authors.forename: Ken
authors.initials: K
authors.lastname: Takizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kimata
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress; D017353:Gene Deletion; D005800:Genes, Fungal; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D050976:Basic-Leucine Zipper Transcription Factors; D019086:Bridged Bicyclo Compounds, Heterocyclic; C091341:HAC1 protein, S cerevisiae; C112936:MYO1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D053778:Thiazolidines; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains; C037067:latrunculin A; D004229:Dithiothreitol