A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome
Graduate School of Biomedical Sciences; Department of Neuroscience; Department of Cell Biology
Medical Subject Headings
Animals; Cells, Cultured; Dendrites; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; Green Fluorescent Proteins; Hippocampus; In Situ Hybridization, Fluorescence; Kinesin; Mice; Mice, Knockout; Microscopy, Video; Models, Biological; Protein Structure, Tertiary; Pseudopodia; *RNA Transport; RNA, Messenger; Sulfuric Acid Esters
Life Sciences | Medicine and Health Sciences
The function of local protein synthesis in synaptic plasticity and its dysregulation in fragile X syndrome (FXS) is well studied, however the contribution of regulated mRNA transport to this function remains unclear. We report a function for the fragile X mental retardation protein (FMRP) in the rapid, activity-regulated transport of mRNAs important for synaptogenesis and plasticity. mRNAs were deficient in glutamatergic signaling-induced dendritic localization in neurons from Fmr1 KO mice, and single mRNA particle dynamics in live neurons revealed diminished kinesis. Motor-dependent translocation of FMRP and cognate mRNAs involved the C terminus of FMRP and kinesin light chain, and KO brain showed reduced kinesin-associated mRNAs. Acute suppression of FMRP and target mRNA transport in WT neurons resulted in altered filopodia-spine morphology that mimicked the FXS phenotype. These findings highlight a mechanism for stimulus-induced dendritic mRNA transport and link its impairment in a mouse model of FXS to altered developmental morphologic plasticity.
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Citation: Dev Cell. 2008 Jun;14(6):926-39. Link to article on publisher's site
Dictenberg, Jason B.; Swanger, Sharon A.; Antar, Laura N.; Singer, Robert H.; and Bassell, Gary J., "A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome" (2008). GSBS Student Publications. Paper 1516.