Muscle specific fragile X related protein 1 isoforms are sequestered in the nucleus of undifferentiated myoblast.

Publication Type:

Journal Article


BMC Genet, Volume 1, p.4 (2000)


Amino Acid Sequence, Animals, Antibodies, Monoclonal, Cell Differentiation, Cell Line, Cell Nucleus, Epitopes, Fragile X Syndrome, Immunohistochemistry, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Muscle Development, Muscle, Skeletal, Myoblasts, Organ Specificity, Polyribosomes, Protein Isoforms, Rabbits, RNA-Binding Proteins


<p><b>BACKGROUND: </b>The family of Fragile X Mental Retardation Proteins is composed of three members: Fragile Mental Retardation 1, Fragile X Related 1 and X Related 2 proteins. These proteins are associated with mRNPs within translating ribosomes and have the capacity to shuttle between the nucleus and the cytoplasm. Great attention has been given to FMRP due to its implication in human hereditary mental retardation while FXR1P and FXR2P have only recently been studied.</p><p><b>RESULTS: </b>Using antibodies directed against several epitopes of FXR1P, we have detected protein isoforms generated by small peptides pocket inserts. Four isoforms of MW 70, 74, 78, 80 kDa are widely distributed in mouse organs, while in striated muscles these isoforms are replaced by proteins of 82 and 84 kDa containing an extra pocket of 27 aa. Expression of these muscle isoforms is an early event during in vitro differentiation of myoblasts into myotubes and correlates with the activation of muscle-specific genes. However, while FXR1P82,84 are associated with cytoplasmic mRNPs in myotubes, they are sequestered in the nuclei of undifferentiated myoblasts. These observations suggest that, in addition to a cytoplasmic function yet to be defined, FXR1P82,84 may play a nuclear role in pre-mRNA metabolism.</p><p><b>CONCLUSIONS: </b>The pattern of subcellular partitioning of FXR1P isoforms during myogenesis is unique among the family of the FXR proteins. The model system described here should be considered as a powerful tool for ongoing attempts to unravel structure-function relationships of the different FMR family members since the potential role(s) of FXR1P as a compensatory factor in Fragile X syndrome is still elusive.</p>

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