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Advisor(s)
Abstract(s)
Differentiation of the presynaptic terminal is a complex and rapid event that normally occurs in spatially specific axonal regions distant from the soma; thus, it is believed to be dependent on intra-axonal mechanisms. However, the full nature of the local events governing presynaptic assembly remains unknown. Herein, we investigated the involvement of the ubiquitin-proteasome system (UPS), the major degradative pathway, in the local modulation of presynaptic differentiation. We found that proteasome inhibition has a synaptogenic effect on isolated axons. In addition, formation of a stable cluster of synaptic vesicles onto a postsynaptic partner occurs in parallel to an on-site decrease in proteasome degradation. Accumulation of ubiquitinated proteins at nascent sites is a local trigger for presynaptic clustering. Finally, proteasome-related ubiquitin chains (K11 and K48) function as signals for the assembly of presynaptic terminals. Collectively, we propose a new axon-intrinsic mechanism for presynaptic assembly through local UPS inhibition. Subsequent on-site accumulation of proteins in their polyubiquitinated state triggers formation of presynapses.
Description
Keywords
Animals Axons Cells, Cultured Hippocampus Luminescent Proteins Microscopy, Fluorescence Polyubiquitin Presynaptic Terminals Proteasome Endopeptidase Complex Proteasome Inhibitors Proteolysis Rats, Wistar Recombinant Fusion Proteins Signal Transduction Synaptic Vesicles Time Factors Time-Lapse Imaging Transfection Ubiquitinated Proteins Ubiquitination Cell Differentiation
Citation
Publisher
The Rockefeller University Press