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

Neurobiology of Disease

Ben A. Oostra¹  Rob Willemsen¹  Femke M.S. de Vrij¹  Maria Rifé¹  Josien Levenga¹  Ronald A.M. Buijsen¹  David L. Nelson²  Hervé Moine³ 

[1] CBG Department of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands;Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA;IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Inserm U596, CNRS UMR7104, Université Louis Pasteur, Collège de France, Illkirch, F-67400 France;

关键词: Fragile X syndrome;    FMRP;    Fmr1;    mRNA transport;    FXR2P;    RNA-granules;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown