F-actin and a type-II myosin are required for efficient clustering of the ER stress sensor Ire1

Cell Struct Funct. 2013 Jul 6;38(2):135-43. doi: 10.1247/csf.12033. Epub 2013 May 10.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actins / genetics
  • Actins / metabolism*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Dithiothreitol / pharmacology
  • Endoplasmic Reticulum Stress*
  • Gene Deletion
  • Genes, Fungal
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Microtubules / genetics
  • Microtubules / metabolism
  • Multigene Family
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Splicing
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Thiazolidines / pharmacology

Substances

  • Actins
  • Basic-Leucine Zipper Transcription Factors
  • Bridged Bicyclo Compounds, Heterocyclic
  • HAC1 protein, S cerevisiae
  • MYO1 protein, S cerevisiae
  • Membrane Glycoproteins
  • RNA, Fungal
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Thiazolidines
  • IRE1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Myosin Heavy Chains
  • latrunculin A
  • Dithiothreitol