Role of microtubules in stress granule assembly: microtubule dynamical instability favors the formation of micrometric stress granules in cells

J Biol Chem. 2009 Dec 25;284(52):36569-36580. doi: 10.1074/jbc.M109.042879. Epub 2009 Oct 19.

Abstract

Following exposure to various stresses (arsenite, UV, hyperthermia, and hypoxia), mRNAs are assembled into large cytoplasmic bodies known as "stress granules," in which mRNAs and associated proteins may be processed by specific enzymes for different purposes like transient storing, sorting, silencing, or other still unknown processes. To limit mRNA damage during stress, the assembly of micrometric granules has to be rapid, and, indeed, it takes only approximately 10-20 min in living cells. However, such a rapid assembly breaks the rules of hindered diffusion in the cytoplasm, which states that large cytoplasmic bodies are almost immobile. In the present work, using HeLa cells and YB-1 protein as a stress granule marker, we studied three hypotheses to understand how cells overcome the limitation of hindered diffusion: shuttling of small messenger ribonucleoprotein particles from small to large stress granules, sliding of messenger ribonucleoprotein particles along microtubules, microtubule-mediated stirring of large stress granules. Our data favor the two last hypotheses and underline that microtubule dynamic instability favors the formation of micrometric stress granules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Sheep
  • Stress, Physiological / physiology*
  • Y-Box-Binding Protein 1

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Ribonucleoproteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human