دورية
EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1knock-out mice
| العنوان: | EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1knock-out mice |
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| المؤلفون: | Su, Ping, Yan, Shuxin, Chen, Kai, Huang, Lianyan, Wang, Le, Lee, Frankie Hang Fung, Zhou, Hang, Lai, Terence Kai Ying, Jiang, Anlong, Samsom, James, Wong, Albert H. C., Yang, Guang, Liu, Fang |
| المصدر: | Molecular Psychiatry; 20240101, Issue: Preprints p1-15, 15p |
| مستخلص: | Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. There is no specific treatment for FXS due to the lack of therapeutic targets. We report here that Elongation Factor 1α (EF1α) forms a complex with two other proteins: Tripartite motif-containing protein 3 (TRIM3) and Murine double minute (Mdm2). Both EF1α-Mdm2 and EF1α-TRIM3 protein complexes are increased in the brain of Fmr1knockout mice as a result of FMRP deficiency, which releases the normal translational suppression of EF1α mRNA and increases EF1α protein levels. Increased EF1α-Mdm2 complex decreases PSD-95 ubiquitination (Ub-PSD-95) and Ub-PSD-95-C1q interaction. The elevated level of TRIM3-EF1α complex is associated with decreased TRIM3-Complement Component 3 (C3) complex that inhibits the activation of C3. Both protein complexes thereby contribute to a reduction in microglia-mediated phagocytosis and dendritic spine pruning. Finally, we created a peptide that disrupts both protein complexes and restores dendritic spine plasticity and behavioural deficits in Fmr1knockout mice. The EF1α-Mdm2 and EF1α-TRIM3 complexes could thus be new therapeutic targets for FXS. |
| قاعدة البيانات: | Supplemental Index |
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Full Text Finder | تدمد: | 13594184 14765578 |
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| DOI: | 10.1038/s41380-023-02396-2 |