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      Fragile X Mental Retardation Protein: Nucleocytoplasmic Shuttling and Association with Somatodendritic Ribosomes

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          Abstract

          Fragile X syndrome, a leading cause of inherited mental retardation, is attributable to the unstable expansion of a CGG-repeat within the FMR1 gene that results in the absence of the encoded protein. The fragile X mental retardation protein (FMRP) is a ribosome-associated RNA-binding protein of uncertain function that contains nuclear localization and export signals. We show here detailed cellular localization studies using both biochemical and immunocytochemical approaches. FMRP was highly expressed in neurons but not glia throughout the rat brain, as detected by light microscopy. Although certain structures, such as hippocampus, revealed a strong signal, the regional variation in staining intensity appeared to be related to neuron size and density. In human cell lines and mouse brain, FMRP co-fractionated primarily with polysomes and rough endoplasmic reticulum. Ultrastructural studies in rat brain revealed high levels of FMRP immunoreactivity in neuronal perikarya, where it is concentrated in regions rich in ribosomes, particularly near or between rough endoplasmic reticulum cisternae. Immunogold studies also provided evidence of nucleocytoplasmic shuttling of FMRP, which was localized in neuronal nucleoplasm and within nuclear pores. Moreover, labeling was observed in large- and small-caliber dendrites, in dendritic branch points, at the origins of spine necks, and in spine heads, all known locations of neuronal polysomes. Dendritic localization, which was confirmed by co-fractionation of FMRP with synaptosomal ribosomes, suggests a possible role of FMRP in the translation of proteins involved in dendritic structure or function and relevant for the mental retardation occurring in fragile X syndrome.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          1 March 1997
          : 17
          : 5
          : 1539-1547
          Affiliations
          [ 1 ]Howard Hughes Medical Institute and Departments of
          [ 2 ]Biochemistry,
          [ 3 ]Pediatrics, and
          [ 4 ] Neurology, Emory University School of Medicine, Atlanta, Georgia 30322
          Article
          PMC6573369 PMC6573369 6573369
          10.1523/JNEUROSCI.17-05-01539.1997
          6573369
          9030614
          822ece80-1179-4600-a527-64ab917d4309
          Copyright © 1997 Society for Neuroscience
          History
          : 23 August 1996
          : 11 November 1996
          : 9 December 1996
          Categories
          Articles

          fragile X syndrome,ribosomes,FMRP,dendritic protein synthesis,RNA binding proteins,trinucleotide repeats,mental retardation,fragile X mental retardation protein

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