The proteasome controls presynaptic differentiation through modulation of an on-site pool of polyubiquitinated conjugates

• Autor(a) principal: Pinto, Maria J.
• Data de Publicação: 2016
• Outros Autores: Alves, Pedro L., Martins, Luís, Pedro, Joana R., Ryu, Hyun R., Jeon, Noo Li, Taylor, Anne M., Almeida, Ramiro D.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/9192
• topic: 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

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.