BMI Progress Reports 2021 // Prof. McCabe's Lab: Soumya Banerjee - The GEF Trio is required for the age-dependent maintenance of synapses

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural ability. Recently, using a novel adult motor synapse preparation, we have investigated Drosophila synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Building upon these observations, we have previously established that miniature neurotransmission is essentially required for the age-dependent structural maintenance of synapses (Banerjee et al. 2021).   Here, we have sought to identify novel factors that can ameliorate age-dependent synapse structural dissolution. From a candidate screen, we identified that the guanine exchange factor (GEF) Trio is required to maintain synaptic architecture during ageing. We show that Trio is localised at neuromuscular presynaptic neurotransmitter release sites and that levels of Trio decline as animals age. We find that premature loss of Trio induces synaptic fragmentation similar to that which occurs during ageing and, importantly, that increasing Trio levels can ameliorate the synaptic degeneration and motor decline of aged animals. Our results reveal that the decline of motor synaptic structures and behavioural capacity during ageing can be deferred.