Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP. - Archive ouverte HAL Access content directly
Journal Articles Journal of Neuroscience Year : 2008

Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP.

Simon P Reeve
  • Function : Author
Xinda Lin
  • Function : Author
Fangfang Jiang
  • Function : Author
Aiyu Yao
  • Function : Author
Zhihua Liu
  • Function : Author
Hui Zhi
  • Function : Author
Kendal Broadie
  • Function : Author
Wei Li
  • Function : Author
Bassem A Hassan
  • Function : Author
Yong Q Zhang
  • Function : Author

Abstract

Fragile X syndrome is the most common form of heritable mental retardation caused by the loss of function of the fragile X mental retardation protein FMRP. FMRP is a multidomain, RNA-binding protein involved in RNA transport and/or translational regulation. However, the binding specificity between FMRP and its various partners including interacting proteins and mRNA targets is essentially unknown. Previous work demonstrated that dFMRP, the Drosophila homolog of human FMRP, is structurally and functionally conserved with its mammalian counterparts. Here, we perform a forward genetic screen and isolate 26 missense mutations at 13 amino acid residues in the dFMRP coding dfmr1. Interestingly, all missense mutations identified affect highly conserved residues in the N terminal of dFMRP. Loss- and gain-of-function analyses reveal altered axonal and synaptic elaborations in mutants. Yeast two-hybrid assays and in vivo analyses of interaction with CYFIP (cytoplasmic FMR1 interacting protein) in the nervous system demonstrate that some of the mutations disrupt specific protein-protein interactions. Thus, our mutational analyses establish that the N terminus of FMRP is critical for its neuronal function.

Dates and versions

hal-00283130 , version 1 (29-05-2008)

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Simon P Reeve, Xinda Lin, Bahar H Sahin, Fangfang Jiang, Aiyu Yao, et al.. Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP.. Journal of Neuroscience, 2008, 28 (12), pp.3221-6. ⟨10.1523/JNEUROSCI.5528-07.2008⟩. ⟨hal-00283130⟩
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