RNA localization is a widely employed mechanism of targeting proteins to their site of function in the cell. RNA transport and local translation within growth cones and dendrites of neurons is known to regulate axon guidance, dendritic spine morphogenesis and synaptic plasticity. RNA localization is therefore fundamental for the development and maintenance of a functional nervous system and is increasingly being linked to learning and memory, as well as neurological disease.
We have recently demonstrated that dendritic mRNAs localize independently and in low copy numbers at distinct synapses and suggested that this contributes to tighter temporal and spatial control of expression in neurons and synapse-specific plasticity. We are currently investigating how synaptic activity regulates targeting of mRNAs to dendrites and synapses, as well as sites of RNA storage and translational repression and/or degradation. To address this question, we are imaging dendritically localized mRNAs and postsynaptic proteins or P bodies and characterize their motility and/or interaction in living or fixed neurons, under different conditions of synaptic activity.
We are down-regulating candidate motor proteins in hippocampal neurons and assessing how this affects transport of mRNAs along dendrites and to synapses.