Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein

Der-I Kao; Georgina M Aldridge; Ivan Jeanne Weiler; William T Greenough

doi:10.1073/pnas.1010564107

Back

Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein

Journal article

Open access

Peer reviewed

Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein

Der-I Kao, Georgina M Aldridge, Ivan Jeanne Weiler and William T Greenough

Proceedings of the National Academy of Sciences - PNAS, Vol.107(35), pp.15601-15606

08/31/2010

DOI: 10.1073/pnas.1010564107

PMCID: PMC2932564

PMID: 20713728

Files and links (1)

url

https://doi.org/10.1073/pnas.1010564107View

Published (Version of record) Open Access

Abstract

Fragile X syndrome is caused by the absence of functional fragile X mental retardation protein (FMRP), an RNA binding protein. The molecular mechanism of aberrant protein synthesis in fmr1 KO mice is closely associated with the role of FMRP in mRNA transport, delivery, and local protein synthesis. We show that GFP-labeled Fmr1 and CaMKIIα mRNAs undergo decelerated motion at 0–40 min after group I mGluR stimulation, and later recover at 40–60 min. Then we investigate targeting of mRNAs associated with FMRP after neuronal stimulation. We find that FMRP is synthesized closely adjacent to stimulated mGluR5 receptors. Moreover, in WT neurons, CaMKIIα mRNA can be delivered and translated in dendritic spines within 10 min in response to group I mGluR stimulation, whereas KO neurons fail to show this response. These data suggest that FMRP can mediate spatial mRNA delivery for local protein synthesis in response to synaptic stimulation.

Biological Sciences

dendritic mRNA targeting

local translation

fragile X syndrome

Details

Title: Subtitle: Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein
Creators: Der-I Kao - Department of Cell and Developmental Biology
Georgina M Aldridge - Beckman Institute
Ivan Jeanne Weiler - Beckman Institute
William T Greenough - Department of Cell and Developmental Biology
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(35), pp.15601-15606
DOI: 10.1073/pnas.1010564107
PMID: 20713728
PMCID: PMC2932564
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 08/31/2010
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984013915702771

Metrics

24 Record Views

115 Times Cited - Web of Science