Emory University    Department of Cell Biology    Imaging Core    Whitehead Biomedical Research Building
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Research Interests of Our Laboratory
The main research interest of our laboratory is to understand the mechanism and function of mRNA transport and local protein synthesis in neurons of the central and peripheral nervous system. We are using in vitro and in vivo models of synaptic activity and nerve injury, as well as mouse models of neurological diseases, to assess the function of mRNA regulation in axon guidance, nerve regeneration and synaptic plasticity. We have a long-standing interest in the mechanism, regulation and function of beta-actin mRNA localization to growth cones of developing axons. More recently, we have been interested how impairments in mRNA regulation may underlie spinal muscular atrophy (SMA) and fragile x syndrome (FXS), two inherited neurological diseases affecting children. Efforts are also underway to evaluate different therapeutic modalities in these mouse models. Our research utilizes a multi-disciplinary approach that involves primary neuronal culture, brain/nerve micro-dissection, viral vectors, fluorescently tagged mRNA and proteins, fluorescence live-cell imaging, and molecular and biochemical methods to isolate and characterize RNA-protein interactions. These studies will provide new insight into molecular and cellular mechanisms important for neuronal development and plasticity, as well as into defects in these pathways that underlie neurological diseases.


Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function
Bassell and Warren, Neuron 2008, 60(2):201-14
The stimulated travels and function of FMRP throughout the neuron
FMRP is in a complex with several translationally arrested mRNAs at the synapse. Following mGluR stimulation, FMRP-target mRNAs are rapidly derepressed, allowing for local translation. A second phase of FMRP-dependent plasticity is shown that involves the subsequent transport of new mRNAs from the cell body into dendrites. (1) Upon mGluR1/5 activation, PP2A is rapidly activated and dephosphorylates FMRP, thereby allowing for (2) local translation of proteins that affect synaptic function. Following mGluR activation, FMRP is rephosphorylated by S6K1 with slower kinetics, leading to translational repression. (3) The local degradation of FMRP by ubiquitination may be involved in translational regulation at the synapse. (4) There may be a retrograde signal (5) possibly involving FMRP shuttling into the nucleus. (6) FMRP acts as a kinesin adapter to facilitate mRNA transport.
(schematic by Sharon Swanger)
 
 
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