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The role of the fragile X mental retardation protein (FMRP) in dendritic mRNA transport


Lack of fragile X mental retardation protein (FMRP) causes fragile X syndrome, a common form of inherited mental retardation. FMRP is an RNA binding protein thought to be involved in translation efficiency and/or trafficking of certain mRNAs. A subset of mRNAs to which FMRP binds with high affinity has been identified. These FMRP-associated mRNAs contain an intermolecular G quartet structure. In neurons, dendrite mRNAs are involved in local synthesis of proteins in response to synaptic activity and this represents a mechanism for synaptic plasticity. Recently, it has been postulated that FMRP is involved in the selective targeting of specificmRNAs containing a G-quartet structure into dendrites and in particular in the vicinity of the synapse. Time-lapse fluorescent microscopy of FMRl-EGFP-transfected PC12 cells illustrated the trafficking of RNA-containing granules into the neuritis with FMRP as a core constituent. The overall aim of this proposal is to study the role of FMRP in dendrite mRNA transport, isolation and characterization of the in vivo target mRNAs FMRP to obtain knowledge about the physiological function of FMRP which will lead to a better understanding of the pathogenesis of the fragile X syndrome. In addition, further identification of mRNA targets of FMRP, especially those mRNAs involved in normal synaptic activity, provides knowledge about the role offer in synaptic plasticity and memory storage. In general, the results might contribute to knowledge about fundamental processes that influence memory and learning in men. The first objective is to develop novel culture methods to obtain neuropterans from mouse brain tissue. The second objective is to study the trafficking and kinetics of FMRP-EGFP granules in dendrites of transientlytransfected primary hippocampal neurons and neuropterans from both wild type and Furl knockout mice using time-lapse co focal microscopy.

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