| Human Molecular Genetics | Pages |
Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis
Introduction
Results
Antibodies against FXR1P isoforms
Complex expression of FXR1Ps in mouse brain and muscle
FXR1P81-84 isoforms are induced during myogenesis in vitro
FXR1P isoforms in myoblasts are associated with polysomal mRNPs
Localization of FXR1P81-84 in muscle
Discussion
Materials And Methods
Cell culture and organs from mouse
Expression vectors
Antibodies to FXR1P and protein analysis
Reverse transcription, PCR and cloning
Sucrose density ultracentrifugation
Immunohistochemistry
Acknowledgements
References
Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis
INTRODUCTION
The fragile X mental retardation syndrome results from transcriptional silencing of the X-linked FMR1 gene and the absence of its encoded protein FMRP (1,2). Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, for fragile X relatives, have been identified (3-5). The overall structure of the FXR1 encoded protein (FXR1P) is very similar to that of FMRP sharing 86% amino acid identity in the central region, and 70% over the N-terminal region. However the C-terminal regions of the two proteins are highly divergent. Molecular cloning revealed the presence of two mRNA isoforms arising from alternative splicing of the FXR1 primary transcript (3,4). Indeed, two proteins were detected with the use of a polyclonal serum directed against Xenopus FXR1P (4,6). Similarly to FMRP, FXR1P contains two KH domains and an RGG box characteristic of RNA binding proteins, as well as nuclear localization and export signal sequences (7-10). It has been reported that FXR1P can interact in vitro with both FMRP and FXR2P (5). In addition, FXR1P binds to RNA homopolymers in vitro and was found associated with ribosomes (6).
Beside the proposed functional protein-protein interactions between FMRP and FXR1P (5), little is known about the expression of the FXR1 encoded proteins. Recently, Tamanini et al. (11) reported a common expression pattern for FMRP and FXR1P in the cytoplasm of differentiated neurons in adult human brain while differential distribution was found in fetal brain. In addition, it was observed that in adult as well as in fetal testis, FMRP and FXR1P are expressed in different cell types. These observations suggest that these related proteins, although structurally very similar and having similar RNA-binding properties, may have independent functions in these tissues during embryonic and adult life (11). However, antibodies recognizing only the longer FXR1P isoform were used in these tissue distribution studies, thus giving partial information on FXR1P expression.
To better define the potential roles of the FXR1Ps with respect to their RNA binding properties and their tissue specificity, we developed antibodies specific to the two FXR1P isoforms. We report here that two major FXR1P isoforms of relative molecular weights of 78 and 70 kDa are expressed in different mammalian cell lines and in the majority of mouse tissues. However, in differentiated muscle tissues, these 78 and 70 kDa isoforms as well as FMRP are absent while we identified novel unexpected FXR1P isoforms and a new FXR1 mRNA variant. Using a myoblast cell line that can be induced to differentiate into myotubes in vitro (12), we show that expression of these novel FXR1P isoforms occurs during myotube differentiation. Finally, we present evidence that the long and short FXR1P isoforms, as well as the new isoforms in differentiating myoblastic cells grown in culture are all associated with messenger ribonucleoparticles (mRNPs) derived from polyribosomes, as was recently observed for FMRP and FXR2P (13,14). In contrast, in mouse muscle tissue the FXR1P isoforms are not associated with polyribosomes and immunohistochemical analyses revealed a localization to structures within the contractile bands.
RESULTS
Antibodies against FXR1P isoforms
To raise antibodies to FXR1P and because of the high degree of amino acid identity between FMRP, FXR1P and FXR2P (3-5), we used two synthetic polypeptides that are localized exclusively in the C-terminus of human FXR1P, covering amino acids 468-488 and 543-562, the latter being specific to the long isoform (Fig.
a)
 b)  |
Figure 1. Characterization of FXR1P isoforms. (a) Amino acid homologies at the C-terminal ends of FXR1P short and long isoforms. The peptides used for immunization of the animals and the corresponding antibodies obtained are indicated above each sequences. (b) Immunoblot analyses of total protein (60 µg) extracted from lymphoblastoid cell lines from a fragile X patient (X) and a normal donor (N) with different antibodies to FMRP and its related proteins. Identical blots were analyzed for the presence of FMRP (mAb1C3), FXR1P (#830 and mAb3FX) and FXR2P (mAbA42).
To test whether #830 and mAb3FX antibodies are also specific to other mammalian FXR1P, protein extracts from human lymphoblastoid and HeLa cells, simian Cos7 and murine 3T3 were prepared and analyzed by immunoblotting. FMRP, as revealed with mAb1C3, was detected in all cell lines, however, at different intensities. HeLa cells contained higher levels than 3T3, followed by lymphoblastoid and Cos cells (Fig.
Figure 2. Comparative analyses of the steady-state levels of FMRP and FXR1P in selected mammalian cell lines. Approximately 50 µg of total protein extracted from: a, human lymphoblasts; b, HeLa S3; c, simian Cos7; and d, murine NIH 3T3 cell lines were analyzed by immunoblotting to determine the respective levels of FMRP, FXR1P78 and 70 and FXR2P. Initial analyses showed that FXR1P78 is widely expressed in different organs in mouse; however, in heart as well as in muscle, a strong signal was observed with a slower mobility than would be expected for FXR1P78. To study this latter immunoreacting form, we compared the expression of FXR1Ps in mouse brain and muscle. These two organs show contrasting expression of FMR1 and FXR1 as high levels of FMR1 mRNA are detected in brain, whereas only trace amounts are observed in muscle (15); on the other hand, high levels of FXR1 mRNA are present in muscle and lower amounts are observed in brain (3). Total protein extracts from mouse brain and from limb skeletal muscle were analyzed by immunoblotting after electrophoretic separation of the proteins onto super-long gels. In addition, we also included in these analyses extracts from FMR1 knockout mice that do not express FMRP (16). Using mAb1C3, high levels of two major FMRP species were revealed at 80 and 78 kDa (Fig. Figure 3. Comparative analyses of steady-state levels of FMR1 and FXR1 proteins in brain and skeletal muscle. Equal amounts of proteins (~40 µg) obtained from normal (N) and knockout (K-o) mice brain (B) and limb muscle (M) were separated onto super-long (23 cm) gels and processed for immunoblot analysis with the indicated antibodies. Based on the results reported above, we conclude first that the slower migrating bands previously detected with mAb1C3 in muscle (15) do in fact correspond to a closely related FMRP homologue which turned out to be an unpredicted novel form of FXR1P. Due to the fact that high levels of this isoform are present in muscle, even a slight reaction with mAb1C3 could give rise to the observed signal. Since mAb1C3 recognizes an, as yet unknown, epitope in the first 114 amino acids at the N-terminus of FMRP (10), it is conceivable that it also recognizes, with much less affinity, similar but incomplete motifs that are present in FXR1P due to the high level of amino acid homology between the two proteins. Secondly, we also conclude that the expression pattern of the FXR1P isoforms in mouse is more complex than seen for proteins from the different cell lines as depicted in Figures One possible explanation for the presence of the super-FXR1P isoforms in muscle was the expression of an FXR1P mRNA variant other than the known short and long isoforms (3,4). To test for this possibility, we compared the expression of splice variants in human brain and muscle RNA using RT-PCR with primers specific to the FXR1 cDNA ends (see Materials and Methods). Since the generated fragment of ~1.8 kb obtained with muscle RNA was slightly longer than that obtained with brain RNA, it was cloned, sequenced and compared with the short and long FXR1 sequences reported by Siomi et al. (4). An insertion of 81 bp was observed starting at position 1615 according to the numbering of Siomi et al. (Fig. Figure 4. Nucleotide sequence analysis of the additional exon found in a human skeletal muscle FXR1 cDNA obtained by RT-PCR. The 81 bp insertion is shown in (a) in capital letters, as well as the flanking sequences starting at nucleotide 1609 according to Siomi et al. numbering (4). The corresponding deduced 27 amino acid sequence is shown in (b) and is compared with the long and short FXR1P known isoforms (3,4). To test the hypothesis that expression of the FXR1P81-84 isoforms could correlate with differentiation of muscular cells, we used the myoblastic cell line C2C4 that can be induced to differentiate into multinucleated myotubes in vitro (12). As shown after staining with DAPI, nuclei from normal proliferating cells display a normal round shape in single cells (Fig. Figure 5. Differential expression of FMRP and FXR1P isoforms during myotube formation in C2C4 myoblastic cell line. Control and insulin-stimulated cultures were fixed and nuclei stained with DAPI and microphotographs taken under epifluorescence illumination. The lower panels correspond to immunoblot analyses of total extracted proteins for FMRP (mAb1C3), FXR1P78 (#830) and FXR1P70 (mAb3FX). Note the decrease of FMRP as well as of both long and short FXR1P isoforms in stimulated cultures and the appearance of the newly expressed FXR1P81-84 isoforms. Given the association of FMRP with polyribosomes as observed in different cell lines, in neurons and in synaptoneurosomes (13,14,19-21) we asked whether the closely related homologue FXR1P, including the new isoforms, would be found associated with mRNP engaged in the translational machinery. Initial analyses using HeLa and lymphoblastoid cells clearly showed that FXR1P70 and P78 cofractionated with polyribosomes. To study FXR1P81-84, post-nuclear supernatants were prepared from non-induced as well as from insulin-stimulated C2C4 cultures and were analyzed by sedimentation velocity through sucrose density gradients. Comparative analyses of the UV profiles obtained after fractionation of the sucrose gradients showed that stimulated cells contained higher amounts of polyribosomes than non-induced cultures with a specific increase in heavy sedimenting polyribosomes (Fig. Figure 6. FXR1P isoforms cofractionate with polyribosomes in the myoblastic cell line C2C4. Aliquots containing ~12 A260 units of post-nuclear supernatants from non-induced control (Control) and insulin-stimulated (Stimulated) cultures were analyzed by sedimentation velocity through sucrose density gradients. (a) UV profiles. Each collected fraction from gradients containing MgCl2 (b) or EDTA (c) was analyzed for the presence of FXR1P78 and P81-84 using antiserum #830. The results reported in Figure Post-nuclear supernatants were prepared from brain and muscle limb lysates and analyzed by velocity sedimentation through sucrose gradients, and each collected fraction was subjected to immunoblot analysis using antiserum #830. In brain extracts, FXR1P78 was detected in fractions containing polyribosomes (Fig. Figure 7. Differential sedimentation properties of FXR1P isoforms in mouse brain and skeletal muscle. Post-nuclear supernatants obtained from brain and limb muscle were analyzed by sedimentation velocity through sucrose density gradients. The collected fractions were assayed for the presence of FXR1P78 and P81-84 using antiserum #830. To determine in situ the localization of FXR1P in muscle, serial longitudinal sections from adult mouse limb were processed for immunostaining using antiserum #830 and mAb3FX. As control, we used brain sections as well as mAb1C3 to reveal FMRP. As expected, intense cytoplasmic staining for FMRP was obtained in neuron-rich regions (11,20,24) as seen in sections from the pons structure in the brain stem, where several of these cells were also positive for FXR1P (Fig. Figure 8. Comparative immunostaining of FMRP and FXR1P in mouse brain and muscle. Paraffin-embedded tissue serial sections were reacted with mAb1C3 (a, c and e) or antiserum #830 (b, d and f) followed by biotinylated secondary antibodies and a streptavidin-peroxidase conjugate, and stained with the AEC chromogen. Note that FMRP and FXR1P are coexpressed in some of the neuronal cells at the level of the pons structure (a and b)as seen in serial sections. In muscle tissues, no FMRP is detected (c), and FXR1P stainings are observed adjacent and apposed to the contractile myofibrillar structures (d). Magnifications of selected areas from (c) and (d) are shown in (e and f). Scale bars: a and b, 100 µm; c and d, 40 µm; e and f, 10 µm. FMRP was the first identified member of a novel family of cytoplasmic mRNA-binding proteins that now includes the two related FXR1 and FXR2 proteins (3-5). Striking amino acid identity exists between these three proteins, and the key RNA-binding domains KH1, KH2 and RGG as well as the two NLS and NES sequences are conserved suggesting that these proteins might have analogous functions in cellular processes such as mRNA transport and/or metabolism (4-7,13,19-21,27). In the present study, we show that similarly to their closely related homologues FMRP and FXR2P, two major FXR1P isoforms of 70 and 78 kDa, are associated with mRNPs derived from polyribosomes in extracts from the C2C4 cell line as well as from mouse brain. In contrast, in differentiated muscle both FXR1P78 and P70 are not detected while novel unpredicted 81-84 kDa forms of FXR1P are expressed. The replacement of these latter isoforms by the new isoforms is clearly apparent during myogenesis of the myoblastic cell line C2C4 that can be differentiated in vitro into myotubes. Since a comparative study of FXR1P levels in different cell lines showed that FXR1P is expressed at very low levels in lymphoblastoid cells as compared with other cell lines such as HeLa or NIH 3T3, it is conceivable that FXR1P contributes to some degree to the signals observed with mAb1C3 at the level of the minor FMRP isoforms in certain cell types other than lymphoblasts. These conclusions are strengthened by the fact that mAb1C3, considered to be specific to FMRP, slightly crossreacts with FXR1Ps as observed in extracts from brain and muscle from knockout mice. Recent results from Tamanini et al. (11) showed localization of FMRP, FXR1P and FXR2P in differentiated neurons in adult human, while differential distributions for each protein were found in fetal brain as well as in testis. The authors strongly suggest that independent tissue functions for each of the three FMR-related proteins might be expected. Using different model systems, namely brain and muscle, we observed that while FMRP and FXR1P are coexpressed in neurons in brain, a completely different picture is observed in muscle. No FMRP is detected and strong immunoreactions are observed with #830 and mAb3FX in muscle; however, the detected antigens are new isoforms of relative higher molecular weights. They most probably correspond to products of novel alternative spliced FXR1 mRNA that would retain the protein epitopes common to the short and long protein isoforms. Indeed, we identified in muscle RNA a new FXR1 splice variant containing an additional 81 bp, which can account for the increase in the MW observed for FXR1P81-84. The observation that in muscle extracts FXR1P81-84 is not associated with polyribosomes and is localized in the myocontractile structures, suggests that in terminal differentiated muscle FXR1P may have a function other than that of the possible control of mRNA transport or translation that has been proposed for the FMRP and FXR family members (4-7,13,19-21,27). Understanding these complex and puzzling modifications will hopefully allow us to propose a function for the FXR1P new isoforms in muscle biology. Studies on the FMR-related family may hold further surprises. The mouse myogenic cell line C2C4, a subclone of the mouse skeletal muscle cell line C2 (12,28), was routinely maintained at low cell density in Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% fetal bovine serum (FBS) plus antibiotics (100 U/ml penicillin, 50 µg/ml streptomycin). Cultures were usually initiated with 5 × 103 cells in 100 mm diameter petri dishes. After 4 days of culture, differentiation was induced by replacing the medium with DMEM containing 0.2% dextran-coated charcoal-treated FBS and 10-6 M insulin (18). Lymphoblastoid cell lines established by Epstein-Barr virus transformation were grown in RPMI medium supplemented with 10% FBS and antibiotics. HeLa (strain S3), NIH 3T3 and Cos7 cells were propagated and maintained in DMEM containing antibiotics and 5% FBS. Adult (3 months old) MF1 mice were killed by Isoflurane (Schein, Ontario, Canada) vapors and brain and limb skeletal muscles were removed and either placed in phosphate-buffered saline (PBS) or immediately frozen in liquid nitrogen and kept at -80°C. FXR1 expression vectors corresponding to the entire length of the long and short FXR1 mRNA isoforms (3,4) were obtained by cloning RT-PCR fragments generated from poly(A)+ mRNA from HeLa cells into the pTL1 expression vector (29). cDNA from FXR2 (5) was also cloned in the same vector. All clones obtained by PCR were controlled by sequencing. For monoclonal and polyclonal antibodies production, we used a synthetic polypeptide corresponding to a sequence common to the short and the long (LKDPDSNPYSLLDNTESDQT) FXR1P isoforms, and another (RAESQSRQRNLPRETLAKNK) specific to the long isoform (3,4). These sequences are not present in FMRP but are conserved in FXR1P from human to Xenopus (4). The peptides were coupled to ovalbumine (ovalbumine-MBS; Aldrich) and purified from the free polypeptides before use for immunization of mice and rabbits using standard protocols. Total proteins from growing cells in subconfluent cultures and from brain and muscle were prepared essentially as described (15) with slight modifications. Cells in culture and tissues were homogenized in 3-fold concentrated SDS-lysis buffer containing 204 mM Tris-HCl, pH 9.0, 6% SDS, 15% [beta]-mercaptoethanol and 45% glycerol. The viscous extracts were heat denatured in a boiling bath for 5 min followed by extensive (2-4 min) sonication without cooling to shear the DNA. Insoluble materials were removed by centrifugation at 17 000 g for 15 min. Protein concentration was determined using the Bradford method after TCA precipitation. Samples were then adjusted to 1× SDS-lysis buffer by dilution with bi-distilled water. Proteins were separated by electrophoresis onto long (13 cm separating gel) or super long (23 cm) polyacrylamide gels (7.5% acrylamide) and then electrotransferred onto 0.45 µm nitrocellulose membranes (Bio-Rad). Immunodetection was performed using mAb1C3 for FMRP (24), mAb3FX and rabbit polyclonal #830 for FXR1P (diluted at 1:2000 and 1:50 000, respectively) and mAbA42 for FXR2P (5). Immunoreaction was detected using peroxidase-conjugated secondary antibodies followed by the ECL reaction. Particular attention was given to the choice of the secondary horseradish peroxidase-labeled anti-mouse Ig since we observed that even in the absence of the primary antibodies, different batches of sheep, goat or rabbit anti-mouse Ig from different suppliers resulted in non grata background signals in the vicinity of the 70 and 57 kDa area in extracts obtained from mouse tissues, making the interpretation of the results extremely hazardous. We found that donkey anti-mouse IgG (H+L) (Jackson ImmunoResearch, code 715-035-150) resulted in the cleanest results since it only slightly recognizes endogenous IgG heavy chains (55-57 kDa) present in mouse tissue extracts. Reverse transcription was performed on 5 µg of total human skeletal muscle RNA (purchased from Clontech, Palo Alto, CA) with oligo(dT) primers. One-tenth of the resulting reaction was used to perform a PCR with the following oligonucleotides: 5[prime]-GGGGCTTTCTACAAGGGATT-3[prime] and 5[prime]-ACCATTCAGGACTGCTGCTT-3[prime]. The PCR product of ~1.8 kb was cloned into the pCRII plasmid using the TA Cloning Kit (Invitrogen, CA) and sequenced with the T7 Sequenase V2 Kit (Amersham). Brain and limb muscle from adult MF1 mice were rapidly removed from animals and finely minced in PBS buffer. The fragments were homogenized in a solution containing 10 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1.5 mM MgCl2, 100 mM NaF, 10 ng/ml aprotinin, 1 mM phenylmethylsulfonyl fluoride, 1 mM DTT, 10 U/ml RNasin (Pharmacia) and 0.5% Nonidet P-40. For cell cultures, the monolayers were washed three times with ice-cold PBS, and 3-5 × 106 cells were lysed in 1 ml of the same buffer used for organs. The lysates were further homogenized by passage through hypodermic needles and a post-nuclear fraction was obtained after centrifugation at 10 000 r.p.m. for 10 min. All manipulations were carried out at 4°C. Aliquots of 1 ml of cytoplasmic extracts, with an OD260 of 12-16, were analyzed by sedimentation velocity in 15-45% (w/w) linear sucrose gradients made up in 25 mM Tris-HCl, pH 7.4, 100 mM KCl, 5 mM MgCl2 unless otherwise indicated. After centrifugation in a Sorval TH-641 rotor for 2 h at 38 000 r.p.m. and 4°C, gradients were fractionated by upward displacement using an Isco UA5 flow-through spectrophotometer set at 254 nm and connected to a gradient collector. Each fraction was denatured with a 3-fold concentrated SDS-lysis buffer and subjected to immunoblot analysis (19). Brain and limb muscle were fixed in 4% paraformaldehyde in PBS for 18 h at 4°C. After dehydration in ethanol, tissues were embedded in paraffin. Five micrometre serial sections were processed for deparaffinization and for microwave oven treatments as described (24). Endogenous peroxidase was inhibited by a 60 min treatment with 0.5% H2O2 solution in PBS, then sections were incubated for 18 h at 4°C with the different antibodies. Bound Abs were reacted with biotinylated secondary antibodies followed by a streptavidin-peroxidase conjugate and staining with the AEC chromogen (Histomouse-SP Kit; Zymed, CA). The slides were counterstained with hematoxylin and mounted in GVA Mount (Zymed). Antibodies used here were: mAb1C3 (24; dilution of the hybridoma supernatant 1:2); mAb3FX (dilution 1:500); antiserum #830 (dilution 1:2000). We are indebted to Y. Lutz and G. Duval for the production of the antibodies. We are grateful to A. Hoogeveen and B. Oostra for providing us with the FMR1 knockout mouse organs, to M. Siomi and G. Dreyfuss for the A42 antibody, and S. Kozma and A. Ziemiecki for anti-ribosomes antibodies. We appreciate the helpful discussions with Y. Labelle and R.M. Tanguay. This work was supported mainly by the Natural Sciences and Engineering Research Council of Canada and the Fonds de recherche en santé du Québec and in part by the Canadian Genetic Diseases Network (to the Québec team) and the Institut National de la Santé, the Centre National de la Recherche Scientifique and the Hôpital Universitaire de Strasbourg (to the Strasbourg team). Lymphoblastoid cell lines were established at the Banque Lymphoblastique du Réseau de Génétique Appliquée du Québec. B.B. is supported by a fellowship from the Commission of the European Communities, F.R. is a Scientist of the Medical Research Council of Canada.
Complex expression of FXR1Ps in mouse brain and muscle
FXR1P81-84 isoforms are induced during myogenesis in vitro
FXR1P isoforms in myoblasts are associated with polysomal mRNPs
Localization of FXR1P81-84 in muscle
DISCUSSION
MATERIALS AND METHODS
Cell culture and organs from mouse
Expression vectors
Antibodies to FXR1P and protein analysis
Reverse transcription, PCR and cloning
Sucrose density ultracentrifugation
Immunohistochemistry
ACKNOWLEDGEMENTS
REFERENCES
This article has been cited by other articles:
This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 13 Nov 1998
Copyright©Oxford University Press, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
L Davidovic, S Sacconi, E G Bechara, S Delplace, M Allegra, C Desnuelle, and B Bardoni
Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients
J. Med. Genet.,
October 1, 2008;
45(10):
679 - 685.
[Abstract]
[Full Text]
[PDF]
E. Bechara, L. Davidovic, M. Melko, M. Bensaid, S. Tremblay, J. Grosgeorge, E. W. Khandjian, E. Lalli, and B. Bardoni
Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure
Nucleic Acids Res.,
January 12, 2007;
35(1):
299 - 306.
[Abstract]
[Full Text]
[PDF]
I. Hofmann, M. Casella, M. Schnolzer, T. Schlechter, H. Spring, and W. W. Franke
Identification of the Junctional Plaque Protein Plakophilin 3 in Cytoplasmic Particles Containing RNA-binding Proteins and the Recruitment of Plakophilins 1 and 3 to Stress Granules
Mol. Biol. Cell,
March 1, 2006;
17(3):
1388 - 1398.
[Abstract]
[Full Text]
[PDF]
M.-E. Huot, N. Bisson, L. Davidovic, R. Mazroui, Y. Labelle, T. Moss, and E. W. Khandjian
The RNA-binding Protein Fragile X-related 1 Regulates Somite Formation in Xenopus laevis
Mol. Biol. Cell,
September 1, 2005;
16(9):
4350 - 4361.
[Abstract]
[Full Text]
[PDF]
M. Castets, C. Schaeffer, E. Bechara, A. Schenck, E. W. Khandjian, S. Luche, H. Moine, T. Rabilloud, J.-L. Mandel, and B. Bardoni
FMRP interferes with the Rac1 pathway and controls actin cytoskeleton dynamics in murine fibroblasts
Hum. Mol. Genet.,
March 15, 2005;
14(6):
835 - 844.
[Abstract]
[Full Text]
[PDF]
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]
E. W. Khandjian, M.-E. Huot, S. Tremblay, L. Davidovic, R. Mazroui, and B. Bardoni
Biochemical evidence for the association of fragile X mental retardation protein with brain polyribosomal ribonucleoparticles
PNAS,
September 7, 2004;
101(36):
13357 - 13362.
[Abstract]
[Full Text]
[PDF]
B. Engels, S. van 't Padje, L. Blonden, L.-a. Severijnen, B. A. Oostra, and R. Willemsen
Characterization of Fxr1 in Danio rerio; a simple vertebrate model to study costamere development
J. Exp. Biol.,
September 1, 2004;
207(19):
3329 - 3338.
[Abstract]
[Full Text]
[PDF]
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]
R. Mazroui, M.-E. Huot, S. Tremblay, N. Boilard, Y. Labelle, and E. W. Khandjian
Fragile X Mental Retardation protein determinants required for its association with polyribosomal mRNPs
Hum. Mol. Genet.,
December 1, 2003;
12(23):
3087 - 3096.
[Abstract]
[Full Text]
[PDF]
R. Willemsen, M. Hoogeveen-Westerveld, S. Reis, J. Holstege, L.-A. W.F.M. Severijnen, I. M. Nieuwenhuizen, M. Schrier, L. van Unen, F. Tassone, A. T. Hoogeveen, et al.
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome
Hum. Mol. Genet.,
May 1, 2003;
12(9):
949 - 959.
[Abstract]
[Full Text]
[PDF]
Y. De Diego Otero, L.-A. Severijnen, G. van Cappellen, M. Schrier, B. Oostra, and R. Willemsen
Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells
Mol. Cell. Biol.,
December 1, 2002;
22(23):
8332 - 8341.
[Abstract]
[Full Text]
[PDF]
R. Mazroui, M.-E. Huot, S. Tremblay, C. Filion, Y. Labelle, and E. W. Khandjian
Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression
Hum. Mol. Genet.,
November 15, 2002;
11(24):
3007 - 3017.
[Abstract]
[Full Text]
[PDF]
C. J. M. Bontekoe, K. L. McIlwain, I. M. Nieuwenhuizen, L. A. Yuva-Paylor, A. Nellis, R. Willemsen, Z. Fang, L. Kirkpatrick, C. E. Bakker, R. McAninch, et al.
Knockout mouse model for Fxr2: a model for mental retardation
Hum. Mol. Genet.,
March 1, 2002;
11(5):
487 - 498.
[Abstract]
[Full Text]
[PDF]
M.-E. Huot, R. Mazroui, P. Leclerc, and E. W. Khandjian
Developmental expression of the fragile X-related 1 proteins in mouse testis: association with microtubule elements
Hum. Mol. Genet.,
November 1, 2001;
10(24):
2803 - 2811.
[Abstract]
[Full Text]
[PDF]
A. Schenck, B. Bardoni, A. Moro, C. Bagni, and J.-L. Mandel
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P
PNAS,
June 28, 2001;
(2001)
151231598.
[Abstract]
[Full Text]
[PDF]
L. Wan, T. C. Dockendorff, T. A. Jongens, and G. Dreyfuss
Characterization of dFMR1, a Drosophila melanogaster Homolog of the Fragile X Mental Retardation Protein
Mol. Cell. Biol.,
November 15, 2000;
20(22):
8536 - 8547.
[Abstract]
[Full Text]
F. Tamanini, L. L. Kirkpatrick, J. Schonkeren, L. v. Unen, C. Bontekoe, C. Bakker, D. L. Nelson, H. Galjaard, B. A. Oostra, and A. T. Hoogeveen
The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins
Hum. Mol. Genet.,
June 12, 2000;
9(10):
1487 - 1493.
[Abstract]
[Full Text]
[PDF]
A. Schenck, B. Bardoni, A. Moro, C. Bagni, and J.-L. Mandel
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P
PNAS,
July 17, 2001;
98(15):
8844 - 8849.
[Abstract]
[Full Text]
[PDF]
This Article 
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (43)
Request Permissions Google Scholar
Articles by Khandjian, E. W.
Articles by Mandel, J.
Search for Related Content
PubMed
PubMed Citation
Articles by Khandjian, E. W.
Articles by Mandel, J.
Social Bookmarking