NEUROTRAF · Molecular mechanisms of synapto-dendritic cargo trafficking

Activity-dependent modulation of synapses is the core mechanism of synaptic plasticity and underlies learning and memory processes in the brain. Understanding dynamic changes at synapses requires a deeper insight in the molecular machinery involved in the transport and trafficking of postsynaptic proteins. Recent studies suggest that the cytoskeleton (microtubule and actin) and molecular motors (kinesin, dynein and myosin) play an essential role in the targeting and delivery of cargos to synapses. Moreover, it has been shown that defects in synaptic cargo transport are common feature of many human neurodegenerative and psychiatric diseases.One of the limiting factors to study synaptic cargo trafficking in living neurons is the lack of appropriate molecular and imaging tools. Recent developments in super-resolution microscopy as well as the progress made in nanotechnology yield many new possibilities to study synaptic trafficking processes in neurons. In this proposal, we will address key issues in synapto-dendritic protein transport by developing novel molecular tools and imaging systems in living neurons. These tools will be utilized to answer a number of fundamental questions: 1) What is the contribution of specific motor proteins to dendritic transport? 2) Do microtubule motors enter dendritic spines and transport cargos in and out? 3) What is the mechanism of cargo movement between neighboring spines? The expected outcomes of this project will contribute fundamental insights into trafficking processes in neurons and deepen our understanding of the molecular dynamics of synapses.""