Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses.
Proc Natl Acad Sci U S A
; 101(50): 17504-9, 2004 Dec 14.
Article
in En
| MEDLINE
| ID: mdl-15548614
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.
Full text:
1
Database:
MEDLINE
Main subject:
Synapses
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Protein Biosynthesis
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RNA-Binding Proteins
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Neurotransmitter Agents
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Glycine
/
Nerve Tissue Proteins
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2004
Type:
Article
Affiliation country:
United States