Coordinated bi-directional trafficking of synaptic vesicle and active zone proteins in peripheral nerves

Synaptic transmission is mediated by neurotransmitters that are stored in synaptic vesicles (SV) and released at the active zone (AZ). While recent years major progress has been made unraveling molecular machinery responsible for SV docking, fusion exocytosis, mechanisms governing AZ protein trafficking through axons still remain unclear. Here, we performed stop-flow nerve ligation to examine axonal of endogenous proteins. Rat sciatic nerves were collected 1 h, 3 h 8 post processed immunohistochemistry electron microscopy. First, followed transport an integral vesicle protein, SV2A a SV-associated involved trafficking, Rab3a, observed while accumulated on both sides ligation, Rab3a was only noticeable proximal segment ligated indicating trans-membrane displayed bi-directional transport. We then demonstrate multiple proteins accumulate rapidly either side with timescale similar SV2A. Overall, our data uncovers unexpected robust bi-directional, coordinated -trafficking peripheral nerves. This implies pathological disruption will not impair newly synthesized synapse but also affect retrograde transport, leading neuronal dysfunction likely neurodegeneration.