In particular, we are interested in the idea that dendritic protein synthesis may contribute to synaptic plasticity. We are also interested in mRNA and protein trafficking during synaptic plasticity. Messenger RNAs are present in the dendrites of hippocampal neurons and are probably used for local protein synthesis in response to synaptic activity during long-term plasticity. To begin to understand the mechanisms underlying dendritic mRNA targeting, we have cloned a gene from a rat hippocampal cDNA library that is related to Drosophila staufen, a gene critical for the asymmetric targeting of specific mRNAs in oocytes and neuroblasts. Preliminary results of in vitro RNA-binding assays suggest that the recombinant rat Staufen protein can bind to multiple mRNAs present in the dendrites of hippocampal neurons, including CaMKII, TrkB, and Arc.
Immunohistochemistry suggests a similar distribution.
These results are consistent with the hypothesis that rat Staufen is associated with dendritic RNAs in vivo and may be involved in their targeting to dendritic compartments. We are also interested in directly visualizing the synthesis of proteins in dendrites. The cDNA constructs were transfected into cultured hippocampal neurons using biolistics. We are examining the effects of synaptic activity and plasticity on translation of the localized GFP message. We are also examining the role of the cadherin family of cell adhesion molecules in synaptic plasticity.