A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome
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UMass Chan Affiliations
Department of Cell BiologyDepartment of Neuroscience
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-06-10Keywords
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 EstersLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
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.Source
Dev Cell. 2008 Jun;14(6):926-39. Link to article on publisher's siteDOI
10.1016/j.devcel.2008.04.003Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32965PubMed ID
18539120Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.devcel.2008.04.003