The Fragile X mental retardation protein

Brain Res Bull. 2001 Oct-Nov;56(3-4):375-82. doi: 10.1016/s0361-9230(01)00647-5.

Abstract

The clinical features of the Fragile X mental retardation syndrome are linked to the absence of the set of protein isoforms, derived from alternative splicing of the Fragile X mental retardation gene 1 (FMR1), and collectively termed FMRP. FMRP is an RNA binding protein that is part of a ribonucleoprotein particle associated to actively translating polyribosomes, and which can shuttle between nucleus and cytoplasm. Two highly homologous human proteins, FXR1P and FXR2P, share the same domain structure as FMRP, and probably similar functions. The properties of FMRP suggested that it is involved in nuclear export, cytoplasmic transport, and/or translational control of target mRNAs. In particular, it may play a role in regulation of protein synthesis at postsynaptic sites of dendrites, and in maturation of dendritic spines. Efforts are underway to identify the putative specific mRNA targets of FMRP, and study the effect of FMRP absence on the corresponding proteins. Other approaches have led to the identification of proteins that interact with FMRP. Some of them discriminate between FMRP and the homologous FXR1/2P proteins, and may thus be important for defining unique functions of FMRP that are deficient in Fragile X patients. The physiological functions of FMRP are notably approached through the study of a FMR1 knock-out mouse model. The recent identification in Drosophila melanogaster of genes encoding homologs of FMRP/FXRP and of their interacting proteins, open the way to use of Drosophila genetics to study FMRP function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics*
  • RNA-Binding Proteins*
  • Trinucleotide Repeats

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein