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Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17504-9. Epub 2004 Nov 17.

Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses.

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1
Beckman Institute, Neuroscience Program, and Departments of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. i-weiler@uiuc.edu

Abstract

Fragile X mental retardation is caused by absence of the RNA-binding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1-knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo. This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome.

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PMID:
15548614
PMCID:
PMC536018
DOI:
10.1073/pnas.0407533101
[Indexed for MEDLINE]
Free PMC Article

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