The mechanism of mRNA transport and localised translation during axis specification and synaptic plasticity. (360G-Wellcome-096144_Z_11_Z)

Intracellular transport of mRNA and its localised translation are common and efficient mechanisms of restricting protein distribution during axis specification in oocytes. They are important for local regulation at the periphery of neurons, during long term memory, synaptic plasticity and are implicated in neurodegenerative diseases. We have discovered conserved trans-acting proteins that bind to the gurken (TGF-alpha) mRNA localisation signal and are required for its localisation and translati onal regulation during Drosophila oocyte axis specification. These include Syncrip, which is conserved in mammals and is complexes with transcripts at hippocampal dendrites. We have shown that Syncrip plays a central role in regulating the translation of localised transcripts, including discs large (PSD-95 in mammals) in neuromuscular synapses. We will use a combination of in vivo and in vitro approaches to characterize the roles of these factors in gurken mRNA localisation and translational reg ulation. We will then elucidate the equivalent functions of Syncrip and its partner trans-acting factors and downstream targets in the neuromuscular junction during synaptic plasticity. Finally, we will search for new transcripts that are localised at the neuromuscular synapse and investigate their mechanism of localisation and function in assembling and regulating the synapse.