Dynein motor contributes to stress granule dynamics in primary neurons

Neuroscience. 2009 Mar 17;159(2):647-56. doi: 10.1016/j.neuroscience.2008.12.053. Epub 2009 Jan 3.

Abstract

Mobilization and translation of mRNAs, two important events believed to involve stress granules (SGs), in neurons are important for their survival and activities. However, the formation and disassembly of SGs in neurons remains unclear. By using an arsenite-induced neuronal stress model of rat primary spinal cord neuron cultures, we demonstrate the formation of SGs that contain common SG components and RNAs in both stressed neuronal cell bodies and their neurites. By employing small interfering RNA (siRNA) knockdown, we discovered that dynein motor subunit localizes in SG, and is important for SG assembly in neurons. Under stress, dynein motor subunit also facilitates translational repression and enhances the formation and integrity of SG in neurons. By blocking the energy source of dynein motor, both the formation and disassembly of SG are attenuated. These findings demonstrate, for the first time, that dynein motor complex plays a critical role in the dynamics of neuronal SGs, as well as translation of certain mRNAs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenylyl Imidodiphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Antigens, Surface / metabolism
  • Arsenites / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Count / methods
  • Cells, Cultured
  • Cysteine / metabolism
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Dose-Response Relationship, Drug
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Dyneins
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Endopeptidase K / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Indoles
  • Methionine / metabolism
  • Motor Neurons / cytology*
  • Motor Neurons / drug effects
  • Motor Neurons / physiology
  • Nonlinear Dynamics*
  • Protein Subunits / metabolism
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • RNA-Binding Proteins / metabolism
  • Rats
  • Spinal Cord
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology
  • Sulfur Isotopes / metabolism
  • Teratogens / pharmacology
  • Time Factors

Substances

  • Antigens, Surface
  • Arsenites
  • Carrier Proteins
  • Drosophila Proteins
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Enzyme Inhibitors
  • Indoles
  • Protein Subunits
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Sulfur Isotopes
  • Teratogens
  • Tial1 protein, rat
  • Adenylyl Imidodiphosphate
  • DAPI
  • 9-(2-hydroxy-3-nonyl)adenine
  • Methionine
  • Endopeptidase K
  • Dyneins
  • Adenine
  • Cysteine
  • arsenite