A Direct Role for FMRP in Activity-Dependent Dendritic mRNA Transport Links Filopodial-Spine Morphogenesis to Fragile X Syndrome

Jason B. Dictenberg, Sharon A. Swanger, Laura N. Antar, Robert H. Singer, Gary J. Bassell

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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.

Original languageEnglish (US)
Pages (from-to)926-939
Number of pages14
JournalDevelopmental Cell
Volume14
Issue number6
DOIs
StatePublished - Jun 10 2008

Fingerprint

Fragile X Mental Retardation Protein
Fragile X Syndrome
Morphogenesis
Spine
Messenger RNA
Neurons
Plasticity
Kinesin
Kinesis
Pseudopodia
Neuronal Plasticity
Brain
Phenotype
Light

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A Direct Role for FMRP in Activity-Dependent Dendritic mRNA Transport Links Filopodial-Spine Morphogenesis to Fragile X Syndrome. / Dictenberg, Jason B.; Swanger, Sharon A.; Antar, Laura N.; Singer, Robert H.; Bassell, Gary J.

In: Developmental Cell, Vol. 14, No. 6, 10.06.2008, p. 926-939.

Research output: Contribution to journalArticle

Dictenberg, Jason B. ; Swanger, Sharon A. ; Antar, Laura N. ; Singer, Robert H. ; Bassell, Gary J. / A Direct Role for FMRP in Activity-Dependent Dendritic mRNA Transport Links Filopodial-Spine Morphogenesis to Fragile X Syndrome. In: Developmental Cell. 2008 ; Vol. 14, No. 6. pp. 926-939.
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