Nonmuscle myosin IIB links cytoskeleton to IRE1α signaling during ER stress

Dev Cell. 2012 Dec 11;23(6):1141-52. doi: 10.1016/j.devcel.2012.11.006.

Abstract

Here we identify and characterize a cytoskeletal myosin protein required for IRE1α oligomerization, activation, and signaling. Proteomic screening identified nonmuscle myosin heavy chain IIB (NMHCIIB), a subunit of nonmuscle myosin IIB (NMIIB), as an ER stress-dependent interacting protein specific to IRE1α. Loss of NMIIB compromises XBP1s and UPR target gene expression with no effect on the PERK pathway. Mechanistically, NMIIB is required for IRE1α aggregation and foci formation under ER stress. The NMIIB-mediated effect on IRE1α signaling is in part dependent on the phosphorylation of myosin regulatory light chain and the actomyosin contractility of NMIIB. Biologically, the function of NMIIB in ER stress response is conserved as both mammalian cells and C. elegans lacking NMIIB exhibit hypersensitivity to ER stress. Thus, optimal IRE1α activation and signaling require concerted coordination between the ER and cytoskeleton.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cell Line
  • Cytoskeleton / metabolism
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum Stress / genetics
  • Endoplasmic Reticulum Stress / physiology*
  • Endoribonucleases / metabolism*
  • Mice
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Nonmuscle Myosin Type IIB / genetics
  • Nonmuscle Myosin Type IIB / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Regulatory Factor X Transcription Factors
  • Signal Transduction*
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1
  • eIF-2 Kinase / metabolism

Substances

  • DNA-Binding Proteins
  • RNA, Small Interfering
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Ern1 protein, mouse
  • PERK kinase
  • Protein-Serine-Threonine Kinases
  • eIF-2 Kinase
  • Endoribonucleases
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains