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Cited by 511Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchRNA Research and Splicing

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

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Dictenberg, Jason B., Swanger, Sharon A., Antar, Laura N., Singer, Robert H., Bassell, Gary J.·2008·Developmental Cell
DOI 10.1016/j.devcel.2008.04.003PMC PMC2453222
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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.

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  • FMRP regulates dendritic targeting of mRNAs and controls protein synthesis and mRNA decay in neuronal soma and at synapses.

    “FXS is due to loss of function of the RNA-binding protein FMRP (Bagni et al., 2012, Bassell and Warren, 2008), which regulates dendritic targeting of mRNAs (Dictenberg et al., 2008) and controls protein synthesis and mRNA decay in neuronal soma and at synapses (Bassell and Warren, 2008).”

    From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Dictenberg et al., 2008

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Cited by

Sorted by citations

Authors
Dictenberg, J. B., Swanger, S. A., Antar, L. N., Singer, R. H., & Bassell, G. J.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Emory University (US)
Corresponding author
  • Dictenberg, Jason B.
  • Bassell, Gary J.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2008-06
Volume
14
Issue
6
Pages
926-939
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2008.04.003
PMC
PMC2453222
OpenAlex
W2063798177
Cited by
511
References
6
Citations by year
2026: 14 · 2025: 15 · 2024: 21 · 2023: 16 · 2022: 23 · 2021: 36 · 2020: 34 · 2019: 29 · 2018: 20 · 2017: 31 · 2016: 28 · 2015: 24 · 2014: 37 · 2013: 32 · 2012: 43
FWCI
18.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Fragile X Foundation
  • National Institutes of Health (AR-41480, NS051127)
  • FRAXA Research Foundation
  • Dana Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
FMRP, fragile X syndrome, dendritic mRNA transport, kinesin light chain, dendritic localization, synaptogenesis, synaptic plasticity, local protein synthesis, filopodia, dendritic spine morphogenesis, Fmr1 knockout mice, glutamatergic signaling
MeSH terms
Animals, Cells, Cultured, Dendrites, Disease Models, Animal, Fragile X Syndrome, Hippocampus, Models, Biological, Pseudopodia, RNA, Messenger, Sulfuric Acid Esters, Kinesins, In Situ Hybridization, Fluorescence, Protein Structure, Tertiary, Mice, Knockout, Microscopy, Video, RNA Transport, Green Fluorescent Proteins, Mice, Fragile X Messenger Ribonucleoprotein 1

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