Ultrastructural characterisation of a nuclear domain highly enriched in survival of motor neuron (SMN) protein

Exp Cell Res. 2004 Jan 15;292(2):312-21. doi: 10.1016/j.yexcr.2003.08.022.

Abstract

Mutations in the survival of motor neuron (SMN) gene are the major cause of spinal muscular atrophy (SMA). The SMN gene encodes a 38-kDa protein that localises in the cytoplasm and in nuclear bodies termed Gemini of coiled bodies (gems). When visualised by immunofluorescence microscopy, gems often appeared either in close proximity to, or entirely overlapping with coiled (Cajal) bodies (CBs) implying a possible functional relationship between these nuclear domains. With the aim of identifying subnuclear compartments corresponding to gems, we have investigated the intranuclear localisation of SMN and of its interacting protein Gemin2 by immunoelectron microscopy in cultured cells and in liver cells of hibernating dormouse. These antigens are highly enriched in round-shaped electron-dense fibro-granular clusters (EFGCs), which also display a biochemical composition similar to gems visualised by immunofluorescence microscopy. Our data reveal a novel SMN/Gemin2 containing nuclear domain and support the idea that it represents the structural counterpart of gems seen in the light microscope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Compartmentation / physiology*
  • Cell Nucleus / metabolism*
  • Coiled Bodies / metabolism*
  • Coiled Bodies / ultrastructure
  • Cyclic AMP Response Element-Binding Protein
  • Cytoplasmic Granules / metabolism
  • Cytoplasmic Granules / ultrastructure
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Hepatocytes
  • Humans
  • Mice
  • Microscopy, Electron
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism
  • Nerve Tissue Proteins / metabolism*
  • RNA-Binding Proteins
  • SMN Complex Proteins

Substances

  • Cyclic AMP Response Element-Binding Protein
  • GEMIN2 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • Sip1 protein, mouse