MicroRNA control of local synaptic protein synthesis in neuronal dendrites

Lead Research Organisation: University of Bristol


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T008741/1 30/09/2020 29/09/2028
2429514 Studentship BB/T008741/1 30/09/2020 29/09/2024
Description Neuronal signalling events are associated with rapid turnover of the proteome in neuronal synapses. This is partly mediated by small, non-coding RNAs called micro-RNAs (miRNAs) which associate with a protein called Argonaut2 (Ago2) to inhibit translation of nascent protein in the synapse. Following NMDA-stimulation to induce long-term depression, a form of synaptic plasticity leading to the long-term reduction in dendritic spine size and synaptic strength, Ago2 is phosphorylated at residue Y393. This phosphorylation has previously been identified in cell lines via EGFR and Src signalling pathways, where it has been shown to alter the interaction between Ago2 and the miRNA maturation protein Dicer, but has never before been identified in neuronal signalling. Furthermore, early evidence suggests that the phosphorylation of Ago2 at Y393 in unstimulated neurons is facilitated via the Src family kinase Fyn. Fyn has previously been identified as a modulator of spine density and morphology in the cortex of a knock-out mouse model, but no mechanism of the regulation of spine density and morphology has been identified. By over-expressing phospho-mimic and phospho-null Ago2 constructs in cultured primary cortical neurons we have identified a significant upregulation in spine density compared to wild-type controls in the phosphomimic model.
Exploitation Route Both Fyn and Ago2 are associated with neurological disorders. This work contributes towards the understanding of their roles in healthy neurons and can contribute to research in both fundamental biology and biomedical research.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology,Other