Slow Axonal Transport and Presynaptic Targeting of Clathrin Packets

Ganguly, A.; Wernert, F.; Phan, S.; BOASSA, D.; Das, U.; Sharma, R.; Caillol, G.; Han, X.; Yates, J. R.; Ellisman, M.; Leterrier, C.; Roy, S.

doi:10.1101/2020.02.20.958140

bioRxiv · 10.1101/2020.02.20.958140

Slow Axonal Transport and Presynaptic Targeting of Clathrin Packets

Ganguly, A.·Wernert, F.·Phan, S.·BOASSA, D.·Das, U.·Sharma, R.·Caillol, G.·Han, X.·Yates, J. R.·Ellisman, M.·Leterrier, C.·Roy, S.

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Abstract

Clathrin has established roles in endocytosis, with clathrin-cages enclosing membrane infoldings, followed by rapid disassembly and reuse of monomers. However, in neurons, clathrin synthesized in cell-bodies is conveyed into axons and synapses via slow axonal transport; as shown by classic pulse-chase radiolabeling. What is the cargo-structure, and mechanisms underlying transport and presynaptic-targeting of clathrin? What is the precise organization at synapses? Combining live-imaging, mass-spectrometry (MS), Apex-labeled EM-tomography and super-resolution, we found that unlike dendrites where clathrin transiently assembles/disassembles as expected, axons contain stable transport-packets that move intermittently with an anterograde bias; with actin/myosin-VI as putative tethers. Transport-packets are unrelated to endocytosis, and the overall kinetics generate a slow biased flow of axonal clathrin. Synapses have integer-numbers of clathrin-packets circumferentially abutting the synaptic-vesicle cluster, advocating a model where delivery of clathrin-packets by slow axonal transport generates a radial organization of clathrin at synapses. Our experiments reveal novel trafficking mechanisms, and an unexpected nanoscale organization of synaptic clathrin.

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Ganguly, A., Wernert, F., Phan, S., BOASSA, D., Das, U., Sharma, R., Caillol, G., Han, X., Yates, J. R., Ellisman, M., Leterrier, C., Roy, S.. 2020-02-20. Slow Axonal Transport and Presynaptic Targeting of Clathrin Packets. https://doi.org/10.1101/2020.02.20.958140

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