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MBC in Press, published online ahead of print October 31, 2007
Mol. Biol. Cell 10.1091/mbc.E07-06-0583

A more recent version of this article appeared on January 1, 2008
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Submitted on June 19, 2007
Revised on September 14, 2007
Accepted on October 19, 2007

Dynamic Association of the Fragile X Mental Retardation Protein as an mRNP between Microtubules and Polyribosomes

Houping Wang,*{dagger} Jason Dictenberg,{dagger}{ddagger}{sect} Li Ku,* Wen Li,* Gary J. Bassell,|| and Yue Feng*

Departments of *Pharmacology and ||Cell Biology, Emory University School of Medicine, Atlanta, GA 30322; {ddagger}Department of Neuroscience, Rose Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, NY 10461

Monitoring Editor: Marvin P. Wickens

The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein that regulates translation and plays essential roles in synaptic function. FMRP is bound to specific mRNA ligands, actively transported into neuronal processes in a microtubule-dependent manner, and associated with polyribosomes engaged in translation elongation. However, the biochemical relationship between FMRP-microtubule association and FMRP-polyribosome association remains elusive. Here we report that although the majority of FMRP is incorporated into elongating polyribosomes in the soluble cytoplasm, microtubule-associated FMRP is predominantly retained in translationally dormant, polyribosome-free messenger ribonucleoprotein (mRNP) complexes. Interestingly, FMRP-microtubule association is increased when mRNPs are dynamically released from polyribosomes as a result of inhibiting translation initiation. Furthermore, the I304N mutant FMRP that fails to be incorporated into polyribosomes is associated with microtubules in mRNP particles and transported into neuronal dendrites in a microtubule-dependent, DHPG-stimulated manner with similar kinetics to that of wild type FMRP. Hence, polyribosome-free FMRP-mRNP complexes travel on microtubules and wait for activity-dependent translational de-repression at the functional destination. The dual participation of FMRP in dormant mRNPs and polyribosomes suggests distinct roles of FMRP in dendritic transport and translational regulation, two distinct phases that control local protein production to accommodate synaptic plasticity.

{dagger}These authors contributed equally to this work.

{sect}Present address: Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065.

Address correspondence to: Yue Feng (yfeng{at}emory.edu)




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J. A. Ronesi and K. M. Huber
Metabotropic Glutamate Receptors and Fragile X Mental Retardation Protein: Partners in Translational Regulation at the Synapse
Sci. Signal., February 5, 2008; 1(5): pe6 - pe6.
[Abstract] [Full Text] [PDF]


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