Effects of dynein inhibitor on the number of motor proteins transporting synaptic cargos.

Abstract Synaptic cargo transport by kinesin and dynein in hippocampal neurons was investigated by non-invasively measuring the transport force based on non-equilibrium statistical mechanics. Although direct physical measurements such as force measurement using optical tweezers are difficult in an intracellular environment, the non-invasive estimations enabled enumerating force producing units (FPUs) carrying a cargo comprising the motor proteins generating force. The number of FPUs served as a barometer for stable and long-distance transport by multiple motors, which was then used to quantify the extent of damage to axonal transport by dynarrestin, a dynein inhibitor. We found that dynarrestin decreased the FPU for retrograde transport more than for anterograde transport. This result indicates the applicability of the non-invasive force measurements. In the future, these measurements may be used to quantify damage to axonal transport resulting from neuronal diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases.