The role of autophagy in presynaptic protein turnover

ended

Neuronal communication primarily occurs at synapses. Recent studies have suggested a key role for protein synthesis and degradation in the regulation of synaptic structure, function and plasticity by changing the abundance of select synaptic proteins in a spatially confined manner. Remodeling of the synaptic proteome is accomplished by, for example, regulated degradation via the ubiquitin proteasome system or by autophagy. Autophagy has been shown to modulate synaptic vesicle numbers and neurotransmission, yet its exact role in the regulation of synaptic function is poorly understood. The proposed project aims at the dissection of the role of autophagy in synaptic protein turnover. Using combined genetic, biochemical, molecular and cellular biology approaches as well as cutting-edge imaging in neurons I will identify presynaptic proteins that are regulated by autophagy and will define the contribution of autophagy to synapse composition and function. Furthermore, I will determine which mechanisms underlie the selective targeting of presynaptic proteins to the autophagy pathway. Taken together these studies will contribute fundamental knowledge about autophagy in neurons and will provide new insights for understanding how autophagy contributes to synaptic plasticity and protein degradation in health and disease.