Cell Biology

Putting Supplies to Use

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Science  10 Sep 2004:
Vol. 305, Issue 5690, pp. 1535
DOI: 10.1126/science.305.5690.1535a

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that is highly expressed in neurons. Absence of the protein results in fragile X syndrome, the most common form of inherited mental retardation, and, in a mouse knockout, the abnormal development of dendritic spines, which may result in deficits in long-term synaptic plasticity. Previous work has suggested that FMRP regulates the neuronal trafficking messenger RNAs (mRNAs) and represses translation of these mRNAs.

Two groups, Stefani et al. and Khandjian et al., describe the association of FMRP with polyribosomes—large, rapidly sedimenting granules containing mRNAs and ribosomes—and these appear to be actively translating conglomerates because Stefani et al. show that the ribosomes can be released by the translational inhibitor puromycin. A clue to how FMRP might be involved in delivery, repression, and use of its mRNA cargo comes from results reported earlier by Antar et al. Using high-resolution fluorescence microscopy, they show that FMRP-containing granules are localized to dendritic spines and that stimulation, either through KCl depolarization or via metabotropic glutamate receptors, dynamically regulates FMRP localization in dendrites and at synapses. Thus, the apparently contradictory functions of FMRP may simply reflect where in the supply line one looks. — GJC

J. Neurosci. 24, 7272 (2004); Proc. Natl. Acad. Sci. U.S.A. 101, 13357 (2004); J. Neurosci. 24, 2648 (2004).

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