Skip Navigation


Human Molecular Genetics Advance Access originally published online on October 21, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
12/24/3295    most recent
ddg350v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (65)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Ceman, S.
Right arrow Articles by Warren, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ceman, S.
Right arrow Articles by Warren, S. T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 24 3295-3305
DOI: 10.1093/hmg/ddg350
© 2003 Oxford University Press

Phosphorylation influences the translation state of FMRP-associated polyribosomes

Stephanie Ceman1,{dagger},{ddagger}, William T. O'Donnell1,{dagger}, Matt Reed2, Stephana Patton1, Jan Pohl2 and Stephen T. Warren1,*

1Department of Human Genetics and 2Microchemical Facility, Emory University School of Medicine, Atlanta, GA 30322, USA

Received July 28, 2003; Accepted October 6, 2003

Fragile X mental retardation protein, FMRP, is absent in patients with fragile X syndrome, a common form of mental retardation. FMRP is a nucleocytoplasmic RNA binding protein that is primarily associated with polyribosomes. FMRP is believed to be a translational repressor and may regulate the translation of certain mRNAs at the base of dendritic spines in neurons. However, little is known about the regulation of FMRP. Using mass spectrometry and site-directed mutagenesis, we show that FMRP is phosphorylated between residues 483 and 521, N-terminal to the RGG box, both in murine brain and in cultured cells. Primary phosphorylation occurs on the highly conserved serine 499, which triggers hierarchical phosphorylation of nearby serines. FMRP is phosphorylated within 2–4 h of synthesis, however, phosphorylation has no effect on the half-life of the protein. In contrast to the Drosophila ortholog dFxr, the phosphorylation status of mammalian FMRP does not influence its association with specific mRNAs in vivo. However, we find unphosphorylated FMRP associated with actively translating polyribosomes while a fraction of phosphorylated FMRP is associated with apparently stalled polyribosomes. Our data suggest that the phosphorylation may regulate FMRP and that the release of FMRP-induced translational suppression may involve a dephosphorylation signal.

* To whom correspondence should be addressed at: Room 305E Whitehead Building, Department of Human Genetics, 615 Michael St, Atlanta, GA 30322, USA. Tel: +1 4047275979; Fax: +1 4047273949; E-mail: swarren{at}emory.edu

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

{ddagger} Present address:

Department of Cell and Structural Biology, University of Illinois, Urbana, IL 61801, USA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 RNAHome page
A. Cheever and S. Ceman
Phosphorylation of FMRP inhibits association with Dicer
RNA, March 1, 2009; 15(3): 362 - 366.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Fahling, R. Mrowka, A. Steege, K. M. Kirschner, E. Benko, B. Forstera, P. B. Persson, B. J. Thiele, J. C. Meier, and H. Scholz
Translational Regulation of the Human Achaete-scute Homologue-1 by Fragile X Mental Retardation Protein
J. Biol. Chem., February 13, 2009; 284(7): 4255 - 4266.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
J. D. Richter and E. Klann
Making synaptic plasticity and memory last: mechanisms of translational regulation
Genes & Dev., January 1, 2009; 23(1): 1 - 11.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M.-C. Didiot, Z. Tian, C. Schaeffer, M. Subramanian, J.-L. Mandel, and H. Moine
The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer
Nucleic Acids Res., September 1, 2008; 36(15): 4902 - 4912.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
U. Narayanan, V. Nalavadi, M. Nakamoto, G. Thomas, S. Ceman, G. J. Bassell, and S. T. Warren
S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade
J. Biol. Chem., July 4, 2008; 283(27): 18478 - 18482.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Piazzon, F. Rage, F. Schlotter, H. Moine, C. Branlant, and S. Massenet
In Vitro and in Cellulo Evidences for Association of the Survival of Motor Neuron Complex with the Fragile X Mental Retardation Protein
J. Biol. Chem., February 29, 2008; 283(9): 5598 - 5610.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Iacoangeli, T. S. Rozhdestvensky, N. Dolzhanskaya, B. Tournier, J. Schutt, J. Brosius, R. B. Denman, E. W. Khandjian, S. Kindler, and H. Tiedge
On BC1 RNA and the fragile X mental retardation protein
PNAS, January 15, 2008; 105(2): 734 - 739.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
H. Wang, J. B. Dictenberg, L. Ku, W. Li, G. J. Bassell, and Y. Feng
Dynamic Association of the Fragile X Mental Retardation Protein as a Messenger Ribonucleoprotein between Microtubules and Polyribosomes
Mol. Biol. Cell, January 1, 2008; 19(1): 105 - 114.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
U. Narayanan, V. Nalavadi, M. Nakamoto, D. C. Pallas, S. Ceman, G. J. Bassell, and S. T. Warren
FMRP Phosphorylation Reveals an Immediate-Early Signaling Pathway Triggered by Group I mGluR and Mediated by PP2A
J. Neurosci., December 26, 2007; 27(52): 14349 - 14357.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. L. Hayashi, B. S. S. Rao, J.-S. Seo, H.-S. Choi, B. M. Dolan, S.-Y. Choi, S. Chattarji, and S. Tonegawa
Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice
PNAS, July 3, 2007; 104(27): 11489 - 11494.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. S. Muddashetty, S. Kelic, C. Gross, M. Xu, and G. J. Bassell
Dysregulated Metabotropic Glutamate Receptor-Dependent Translation of AMPA Receptor and Postsynaptic Density-95 mRNAs at Synapses in a Mouse Model of Fragile X Syndrome
J. Neurosci., May 16, 2007; 27(20): 5338 - 5348.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. E. Pfeiffer and K. M. Huber
Fragile X Mental Retardation Protein Induces Synapse Loss through Acute Postsynaptic Translational Regulation
J. Neurosci., March 21, 2007; 27(12): 3120 - 3130.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. M. Spencer, E. Serysheva, L. A. Yuva-Paylor, B. A. Oostra, D. L. Nelson, and R. Paylor
Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins
Hum. Mol. Genet., June 15, 2006; 15(12): 1984 - 1994.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
N. Dolzhanskaya, G. Merz, J. M. Aletta, and R. B. Denman
Methylation regulates the intracellular protein-protein and protein-RNA interactions of FMRP.
J. Cell Sci., May 1, 2006; 119(Pt 9): 1933 - 1946.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. Davidovic, E. Bechara, M. Gravel, X. H. Jaglin, S. Tremblay, A. Sik, B. Bardoni, and E. W. Khandjian
The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons
Hum. Mol. Genet., May 1, 2006; 15(9): 1525 - 1538.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Stetler, C. Winograd, J. Sayegh, A. Cheever, E. Patton, X. Zhang, S. Clarke, and S. Ceman
Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp
Hum. Mol. Genet., January 1, 2006; 15(1): 87 - 96.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
H. Wang, A. Iacoangeli, D. Lin, K. Williams, R. B. Denman, C. U.T. Hellen, and H. Tiedge
Dendritic BC1 RNA in translational control mechanisms
J. Cell Biol., December 5, 2005; 171(5): 811 - 821.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Garnon, C. Lachance, S. Di Marco, Z. Hel, D. Marion, M. C. Ruiz, M. M. Newkirk, E. W. Khandjian, and D. Radzioch
Fragile X-related Protein FXR1P Regulates Proinflammatory Cytokine Tumor Necrosis Factor Expression at the Post-transcriptional Level
J. Biol. Chem., February 18, 2005; 280(7): 5750 - 5763.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Aschrafi, B. A. Cunningham, G. M. Edelman, and P. W. Vanderklish
The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain
PNAS, February 8, 2005; 102(6): 2180 - 2185.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Miyashiro and J. Eberwine
Fragile X syndrome: (What's) lost in translation?
PNAS, December 14, 2004; 101(50): 17329 - 17330.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. J. Weiler, C. C. Spangler, A. Y. Klintsova, A. W. Grossman, S. H. Kim, V. Bertaina-Anglade, H. Khaliq, F. E. de Vries, F. A. E. Lambers, F. Hatia, et al.
From the Cover: Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses
PNAS, December 14, 2004; 101(50): 17504 - 17509.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. A. Gabel, S. Won, H. Kawai, M. McKinney, A. M. Tartakoff, and J. R. Fallon
Visual Experience Regulates Transient Expression and Dendritic Localization of Fragile X Mental Retardation Protein
J. Neurosci., November 24, 2004; 24(47): 10579 - 10583.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
H. Wang and H. Tiedge
Translational Control at the Synapse
Neuroscientist, October 1, 2004; 10(5): 456 - 466.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
G. Stefani, C. E. Fraser, J. C. Darnell, and R. B. Darnell
Fragile X Mental Retardation Protein Is Associated with Translating Polyribosomes in Neuronal Cells
J. Neurosci., August 18, 2004; 24(33): 7272 - 7276.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. J. Mientjes, R. Willemsen, L. L. Kirkpatrick, I. M. Nieuwenhuizen, M. Hoogeveen-Westerveld, M. Verweij, S. Reis, B. Bardoni, A. T. Hoogeveen, B. A. Oostra, et al.
Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo
Hum. Mol. Genet., July 1, 2004; 13(13): 1291 - 1302.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. N. Antar, R. Afroz, J. B. Dictenberg, R. C. Carroll, and G. J. Bassell
Metabotropic Glutamate Receptor Activation Regulates Fragile X Mental Retardation Protein and Fmr1 mRNA Localization Differentially in Dendrites and at Synapses
J. Neurosci., March 17, 2004; 24(11): 2648 - 2655.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.