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

Ivan Jeanne Weiler*, Chad C. Spangler, Anna Y. Klintsova, Aaron W. Grossman, Soong Ho Kim, Valerie Bertaina-Anglade, Hooma Khaliq, Froukje E. De Vries, Femke A.E. Lambers, Fatima Hatia, Christine K. Base, William T. Greenough

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)17504-17509
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number50
DOIs
Publication statusPublished - 14 Dec 2004

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