Disruption of microtubules inhibits cytoplasmic ribonucleoprotein stress granule formation

Exp Cell Res. 2003 Nov 1;290(2):227-33. doi: 10.1016/s0014-4827(03)00290-8.

Abstract

Stress granules are RNP-containing particles arising in the cytoplasm in response to environmental stress. They are dynamic structures assembling and disassembling in the cytoplasm very rapidly. We have studied whether the cytoskeleton is involved in the formation of stress granules. Stress granules were induced in CV-1 cells by sodium arsenate treatment and visualized by immunofluorescent staining with antibodies either to the p170 subunit of eIF3 or to poly(A)-binding protein. Treatment with sodium arsenate for 30-120 min led to assembling of stress granules in a majority of CV-1 cells. Disruption of MT array with nocodazole treatment abolished arsenate-induced formation of stress granules. A similar effect was induced by the microtubule-depolymerizing drug vinblastine, though the influence of the microtubule-stabilizing drug paclitaxel was opposite. Nocodazole treatment did not prevent arsenate-induced phosphorylation of the eIF-2alpha factor, essential for stress granule formation, suggesting that the presence of intact MT array is required for granule assembly. Unexpectedly, treatment of cells with the actin filament-disrupting drug latrunculin B slightly enhanced stress granule formation. We propose that stress granule formation is microtubule-dependent process and likely is facilitated by the motor protein-driven movement of individual stress granule components (e.g., mRNP) along microtubules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / drug effects
  • Actins / physiology
  • Animals
  • Arsenates / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cells, Cultured
  • Chlorocebus aethiops / metabolism
  • Cytoplasmic Granules / metabolism*
  • Cytoskeleton / drug effects*
  • Eukaryotic Initiation Factor-3 / metabolism
  • Fibroblasts / metabolism
  • Marine Toxins / pharmacology
  • Microtubules / drug effects
  • Microtubules / physiology*
  • Nocodazole / pharmacology
  • Paclitaxel / pharmacology
  • Phosphorylation / drug effects
  • Prokaryotic Initiation Factor-3 / metabolism
  • Ribonucleoproteins / metabolism*
  • Stress Fibers / metabolism*
  • Thiazoles / pharmacology
  • Thiazolidines
  • Vinblastine / pharmacology

Substances

  • Actins
  • Arsenates
  • Bridged Bicyclo Compounds, Heterocyclic
  • Eukaryotic Initiation Factor-3
  • Marine Toxins
  • Prokaryotic Initiation Factor-3
  • Ribonucleoproteins
  • Thiazoles
  • Thiazolidines
  • messenger ribonucleoprotein
  • Vinblastine
  • sodium arsenate
  • Paclitaxel
  • Nocodazole
  • latrunculin A