Influence of cargo geometry on axonal transport kinetics

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DESCRIPTION (provided by applicant): Proper function of the neuro-muscular system requires the delivery of a variety of cargoes from the neuronal cell body to destinations along the length of the axon via molecular motor-mediated transport. Given the diversity of cargoes, there is a surprising lack of information on how critical variables such as cargo size, motor density, and axonal geometry interact to affect the transport of cargo-motor complexes. The proposed experiments will test hypotheses regarding relationships between cargo size and cargo velocity, cargo run lengths, and the continuity of cargo motion. In addition, hypotheses regarding the effects of physical blockages, such as those found in the pathology of several neurodegenerative diseases, on axonal transport will be tested. Towards the testing of these hypotheses, I propose to 1) quantify the influence of cargo size on transport kinetics by imaging the motion of fluorescent beads of different diameters in cultured neurons, 2) to determine the influence of cargo size on transport kinetics by imaging the transport of vesicles engineered to specified sizes, and 3) To characterize the effects of protein accumulation on transport by introducing aggregated beta-amyloid fibrils into cultured neurons.