Membrane dynamics at the synaptic terminal

Previous and current research
The identification of the mechanisms responsible for membrane sorting and trafficking at the synapse is one of the challenging frontiers of neurobiology. Despite the importance of these processes for neuronal homeostasis, differentiation and survival, they are yet still poorly understood at molecular level. Specific sorting allows the retention of pools of endocytic vesicles at the synapse or their targeting to axonal retrograde transport routes. Retrograde transport pathways allow the cross-talk between the synapse and the soma and are crucial for the physiological transport of neurotrophins and various signalling molecules, and the entry of pathogens in the nervous system. Impairment of the precise balance between anterograde and retrograde axonal transport is thought to be at the basis of severe neurodegenerative pathologies.

Our laboratory aims to provide an integrated approach to the study of neuronal membrane dynamics. In the last year, we have made significant progress in defining the machinery controlling the uptake and sorting of ligands to axonal transport pathways in neurons. We analysed the properties of the retrograde transport compartment in health and disease, highlighting the central role of dynein in the movement of these carriers and in disease progression in an animal model of motor neuron disease. Furthermore, we investigated the function of molecular motors in the trafficking of Kidins220, a neurotrophin receptor regulator in neurons. These studies have been complemented by the analysis of torsinA, a protein that once mutated causes an early-onset dystonia in humans by affecting the targeting of proteins involved in neurotransmitter release.

Future projects
We will continue to investigate the machinery responsible for the uptake and targeting of carriers to the axonal retrograde transport route using the information derived from the proteomic analysis of this compartment in motor neurons. Furthermore, we are developing novel strategies to monitor axonal retrograde transport in vivo and to dissect the steps that control calcium-regulated exocytosis and sorting at the synapse. We are interested in characterising new tools modulating neurotransmission, focusing on proteins and lipids capable of strongly promoting neurotransmitter release.