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Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Reeve, Simon P. Lin, Xinda Sahin, Bahar H. Jiang, Fangfang Yao, Aiyu Liu, Zhihua Zhi, Hui Broadie, Kendal Li, Wei Giangrande, Angela Hassan, Bassem A. Zhang, Yong Q. |
| Copyright Year | 2008 |
| 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. |
| Starting Page | 2282 |
| Ending Page | 2282 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://sourcedb.genetics.cas.cn/yw/zjrc/db/200907/W020090729381832362899.pdf |
| PubMed reference number | 18354025v1 |
| Alternate Webpage(s) | https://doi.org/10.1523/JNEUROSCI.5528-07.2008 |
| DOI | 10.1523/jneurosci.5528-07.2008 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Volume Number | 28 |
| Issue Number | 12 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Amino Acids Cri-du-Chat Syndrome FMR1 protein, human Fragile X Mental Retardation Protein Hereditary Diseases Mammals Missense Mutation Nervous system structure RNA Transport Translational Regulation Two-Hybrid System Techniques mutant newton protein protein interaction |
| Content Type | Text |
| Resource Type | Article |
