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

Geertruida Levenga, Ronald Buijsen, M Rife, H Moine, DL Nelson, Ben Oostra, Rob Willemsen, Femke de Vrij

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18 Citations (Scopus)

Abstract

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_1304N 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. (C) 2009 Elsevier Inc. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)241-250
Number of pages10
JournalNeurobiology of Disease
Volume35
Issue number2
DOIs
Publication statusPublished - 2009

Research programs

  • EMC MGC-02-96-01

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