Title

A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Neuroscience; Department of Cell Biology

Date

6-10-2008

Document Type

Article

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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Dev Cell. 2008 Jun;14(6):926-39. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

18539120