Trafficking Mechanics of Inter-Synaptic Vesicle Exchange Support in Synaptic Transmission

Mature presynapses share proteins with neighboring presynapses via intracellular axonal transport. These proteins are predominantly shared using neurotransmitter carrying synaptic vesicles, through a process called Inter-Synaptic-Vesicle-Exchange (ISVE). Further, ISVE may also support synaptic transmission by providing a pool of vesicles during activity. While the mechanics of axonal synaptic vesicle transport have been studied previously, the capture of vesicles by neighboring presynapses dominate the efficiency of ISVE and the capture process is less understood. In this presentation we will discuss evidence that the structure of the actin presynaptic cytoskeleton, through the ARP2/3 branching complex, is important for vesicle capture. We utilize high-resolution single vesicle fluorescence microscopy in live cells to measure ISVE transport at the nanometer and millisecond scales. We show that acutely inhibiting the ARP2/3 complex results in reduced vesicle capture and synaptic transmission. We also show that acute loss of the actin-based transport motor myosin-V reduces vesicle capture. Lastly, we show how actin structure and myosin-V function mediate activity-dependent capture to support synaptic transmission.