Protein turn over at the synapse and the maintenance of robust neuronal communication.

Synaptic contacts are often located very far away from their cell bodies and they are largely independently coping with the unfolded, dysfunctional proteins that form as a result of repeated reuse and cellular stress. Our hypothesis is that synaptic terminals have adopted specific mechanisms to retain activity over their long lives. Engulfment of cytoplasm by autophagy and degradation would constitute an ideal mechanism to be involved in the maintenance of synaptic health by clearing cellular debris, but at synapses the process is not well-studied. Based on the requirement of autophagy to bend and shape membranes, we propose to capitalize on innovative in vitro liposome-based proteome-wide screening methods and in vivo studies at fruit fly synapses to isolate novel membrane-associated machines that mediate synaptic autophagy. A preliminary screen has already revealed exciting candidates that link membrane deformation to autophagic processes at synapses and we will scrutinize these in detail. Our work not only has the capacity to uncover novel aspects in the regulation of presynaptic function, but it will also reveal mechanisms of synaptic dysfunction in models of neuronal demise.