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

2016Journal article Open access
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dc.contributor.authorPinto, Maria J.
dc.contributor.authorAlves, Pedro L.
dc.contributor.authorMartins, Luís
dc.contributor.authorPedro, Joana R.
dc.contributor.authorRyu, Hyun R.
dc.contributor.authorJeon, Noo Li
dc.contributor.authorTaylor, Anne M.
dc.contributor.authorAlmeida, Ramiro D.
dc.date.accessioned2017-01-10T16:14:44Z
dc.date.available2017-01-10T16:14:44Z
dc.date.issued2016
dc.description.abstractDifferentiation 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1083/jcb.201509039pt_PT
dc.identifier.issn1540-8140
dc.identifier.urihttp://hdl.handle.net/10400.22/9192
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherThe Rockefeller University Presspt_PT
dc.relation.publisherversionhttp://jcb.rupress.org/content/212/7/789pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/pt_PT
dc.subjectAnimalspt_PT
dc.subjectAxonspt_PT
dc.subjectCells, Culturedpt_PT
dc.subjectHippocampuspt_PT
dc.subjectLuminescent Proteinspt_PT
dc.subjectMicroscopy, Fluorescencept_PT
dc.subjectPolyubiquitinpt_PT
dc.subjectPresynaptic Terminalspt_PT
dc.subjectProteasome Endopeptidase Complexpt_PT
dc.subjectProteasome Inhibitorspt_PT
dc.subjectProteolysispt_PT
dc.subjectRats, Wistarpt_PT
dc.subjectRecombinant Fusion Proteinspt_PT
dc.subjectSignal Transductionpt_PT
dc.subjectSynaptic Vesiclespt_PT
dc.subjectTime Factorspt_PT
dc.subjectTime-Lapse Imagingpt_PT
dc.subjectTransfectionpt_PT
dc.subjectUbiquitinated Proteinspt_PT
dc.subjectUbiquitinationpt_PT
dc.subjectCell Differentiationpt_PT
dc.titleThe proteasome controls presynaptic differentiation through modulation of an on-site pool of polyubiquitinated conjugatespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage801pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage789pt_PT
oaire.citation.titleJournal of Cell Biologypt_PT
oaire.citation.volume212pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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