The state of synapses in fragile X syndrome
- PMID: 19325170
- PMCID: PMC2762019
- DOI: 10.1177/1073858409333075
The state of synapses in fragile X syndrome
Abstract
Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure, and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene, which encodes the RNA binding protein, fragile X mental retardation protein (FMRP). Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is present at synapses where it associates with mRNA and polyribosomes. Accumulating evidence finds roles for FMRP in synapse development, elimination, and plasticity. Here, the authors review the synaptic changes observed in FXS and try to relate these changes to what is known about the molecular function of FMRP. Recent advances in the understanding of the molecular and synaptic function of FMRP, as well as the consequences of its loss, have led to the development of novel therapeutic strategies for FXS.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2762019/bin/nihms127816f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2762019/bin/nihms127816f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2762019/bin/nihms127816f3.gif)
Similar articles
-
Metabotropic glutamate receptors and fragile x mental retardation protein: partners in translational regulation at the synapse.Sci Signal. 2008 Feb 5;1(5):pe6. doi: 10.1126/stke.15pe6. Sci Signal. 2008. PMID: 18272470 Review.
-
Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function.Neuron. 2008 Oct 23;60(2):201-14. doi: 10.1016/j.neuron.2008.10.004. Neuron. 2008. PMID: 18957214 Free PMC article. Review.
-
microRNAs and Fragile X Syndrome.Adv Exp Med Biol. 2015;888:107-21. doi: 10.1007/978-3-319-22671-2_7. Adv Exp Med Biol. 2015. PMID: 26663181
-
Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules.PLoS Genet. 2016 Jul 27;12(7):e1006192. doi: 10.1371/journal.pgen.1006192. eCollection 2016 Jul. PLoS Genet. 2016. PMID: 27462983 Free PMC article.
-
Molecular mechanisms of fragile X syndrome: a twenty-year perspective.Annu Rev Pathol. 2012;7:219-45. doi: 10.1146/annurev-pathol-011811-132457. Epub 2011 Oct 10. Annu Rev Pathol. 2012. PMID: 22017584 Review.
Cited by
-
Increased number of excitatory synapsis and decreased number of inhibitory synapsis in the prefrontal cortex in autism.Cereb Cortex. 2024 May 2;34(13):121-128. doi: 10.1093/cercor/bhad268. Cereb Cortex. 2024. PMID: 38696601
-
Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome.Cell. 2023 Dec 21;186(26):5840-5858.e36. doi: 10.1016/j.cell.2023.11.019. Cell. 2023. PMID: 38134876
-
FMRP phosphorylation modulates neuronal translation through YTHDF1.Mol Cell. 2023 Dec 7;83(23):4304-4317.e8. doi: 10.1016/j.molcel.2023.10.028. Epub 2023 Nov 9. Mol Cell. 2023. PMID: 37949069
-
FMRP phosphorylation and interactions with Cdh1 regulate association with dendritic RNA granules and MEF2-triggered synapse elimination.Neurobiol Dis. 2023 Jun 15;182:106136. doi: 10.1016/j.nbd.2023.106136. Epub 2023 Apr 28. Neurobiol Dis. 2023. PMID: 37120096 Free PMC article.
-
The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes.Front Neurosci. 2022 Nov 16;16:1007531. doi: 10.3389/fnins.2022.1007531. eCollection 2022. Front Neurosci. 2022. PMID: 36466176 Free PMC article.
References
-
- Adinolfi S, Ramos A, Martin SR, Dal Piaz F, Pucci P, Bardoni B, Mandel JL, Pastore A. The N-terminus of the fragile X mental retardation protein contains a novel domain involved in dimerization and RNA binding. Biochemistry. 2003;42:10437–10444. - PubMed
-
- Antar LN, Dictenberg JB, Plociniak M, Afroz R, Bassell GJ. Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons. Genes Brain Behav. 2005;4:350–359. - PubMed
-
- Antar LN, Li C, Zhang H, Carroll RC, Bassell GJ. Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses. Mol Cell Neurosci 2006 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical