Ultrastructural analysis of the functional domains in FMRP using primary hippocampal mouse neurons

Neurobiol Dis. 2009 Aug;35(2):241-50. doi: 10.1016/j.nbd.2009.05.004. Epub 2009 May 21.


Fragile X syndrome is caused by lack of the protein FMRP. FMRP mediates mRNA binding, dendritic mRNA transport and translational control at spines. We examined the role of functional domains of FMRP in neuronal RNA-granule formation and dendritic transport using different FMRP variants, including the mutant FMRP_I304N and the splice-variant FMRP_Iso12. Both variants are absent from dendritic RNA-granules in Fmr1 knockout neurons. Co-transfection experiments showed that wild-type FMRP recruits both FMRP variants into dendritic RNA-granules. Co-transfection of FXR2, an FMRP homologue, also resulted in redistribution of both variants into dendritic RNA-granules. Furthermore, the capacity of the variants to transport their mRNAs and the mRNA localization of an FMR1 construct containing silent point-mutations affecting only the G-quartet-structure were investigated. In conclusion, we show that wild-type FMRP and FXR2P are able to recruit FMRP variants into RNA-granules and that the G-quartet-structure in FMR1 mRNA is not essential for its incorporation in RNA-granules.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Fragile X Mental Retardation Protein / chemistry
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Mutation
  • Neurons / cytology
  • Neurons / metabolism*
  • Nucleic Acid Conformation
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • RNA Transport*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transfection


  • FXR2 protein, mouse
  • Fmr1 protein, mouse
  • Protein Isoforms
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein