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Sci. Signal., 5 February 2008
Vol. 1, Issue 5, p. pe6
[DOI: 10.1126/stke.15pe6]

PERSPECTIVES

Metabotropic Glutamate Receptors and Fragile X Mental Retardation Protein: Partners in Translational Regulation at the Synapse

Jennifer A. Ronesi1 and Kimberly M. Huber1*

1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract: Fragile X syndrome (FXS) mental retardation is caused by loss-of-function mutations in an RNA-binding protein, fragile X mental retardation protein (FMRP). Previous studies in patients or animal models of FXS have identified alterations in dendritic spine structure, as well as synaptic plasticity induced by metabotropic glutamate receptors (mGluRs). The translation of multiple messenger RNA (mRNA) targets of FMRP is regulated by mGluRs at synapses. Here, we incorporate data from several studies into a working model of how FMRP regulates mGluR-stimulated protein synthesis and, in turn, regulates protein synthesis–dependent synaptic plasticity. Understanding the complex functions of FMRP at the synapse will lead to a better understanding of the neurobiological underpinnings of mental retardation.

*Corresponding author. Department of Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, NA4.118, Dallas, TX 75390–9011, USA; e-mail, kimberly.huber{at}utsouthwestern.edu

Citation: J. A. Ronesi, K. M. Huber, Metabotropic Glutamate Receptors and Fragile X Mental Retardation Protein: Partners in Translational Regulation at the Synapse. Sci. Signal. 1, pe6 (2008).

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