Question

Fragile x syndrome is most commonly caused by the expansion of over 200 copies of a cgg repeat in the 5′-untranslated region of the fmr1 gene that silences transcription of the gene. the fmrp, which is the fmr1 gene product, is a selective rna-binding protein that negatively regulates local protein synthesis in neuronal dendrites

Answer 1

Fragile X syndrome is the leading cause of hereditary intellectual disability. This syndrome results from the absence of the FMRP protein. FMRP is proposed to regulate, under the control of mGluR-I and other receptors, the expression of proteins important for synaptic plasticity by specifically binding to their mRNA and modulating their translation.

By covalent UV and immunoprecipitation (CLIP) bridging approach coupled with microarray analysis, mRNA has been identified as a unique target of FMRP in cortical neurons. This mRNA encodes a kinase controlling the level of two-second-lipid-messengers important for the remodeling of dendritic spines.

Furthermore, we have shown that kinase-dependent mGluR-I activation is absent in Fmr1 KO neurons, resulting in an alteration of several lipid species in the neuron.

These defects may explain the morphological and functional alterations of dendritic spines, the main cause of Fragile X syndrome.