Dynamic Association of the Fragile X Mental Retardation Protein as a Messenger Ribonucleoprotein between Microtubules and Polyribosomes

• Type of Material: Article
• Authors: Houping Wang, Emory University; Jason B. Dictenberg, Albert Einstein College of Medicine; Li Ku, Emory University; Wen Li, Emory University; Gary Bassell, Emory University; Yue Feng, Emory University
• Language: English
• Date: 2008-01
• Publisher: American Society for Cell Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2007 by The American Society for Cell Biology
• Final Published Version (URL): http://www.molbiolcell.org/content/19/1/105
• Title of Journal or Parent Work: Molecular Biology of the Cell
• ISSN: 1059-1524
• Volume: 19
• Issue: 1
• Start Page: 105
• End Page: 114
• Grant/Funding Information: This work is supported by National Institutes of Health grant 5 P01 HD-35576 (Project III) and Fraxa foundation (to Y.F.), National Institutes of Health grant NS-051127 and the Dana Foundation grant (to G.B.), and a National Fragile X Foundation Basic Sciences Grant (to J.B.D.).
• Research Categories: Biology, Molecular; Biology, Neuroscience; Biology, Cell

Abstract

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, 3,5-dihydroxyphenylglycine-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 derepression at the site of function. 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.