title: Activity-dependent dynamics and sequestration of proteasomes in dendritic spines.
abstract: The regulated degradation of proteins by the ubiquitin proteasome pathway is emerging as an important modulator of synaptic function and plasticity. The proteasome is a large, multi-subunit cellular machine that recognizes, unfolds and degrades target polyubiquitinated proteins. Here we report NMDA (N-methyl-D-aspartate) receptor-dependent redistribution of proteasomes from dendritic shafts to synaptic spines upon synaptic stimulation, providing a mechanism for local protein degradation. Using a proteasome-activity reporter and local perfusion, we show that synaptic stimulation regulates proteasome activity locally in the dendrites. We used restricted photobleaching of individual spines and dendritic shafts to reveal the dynamics that underlie proteasome sequestration, and show that activity modestly enhances the entry rate of proteasomes into spines while dramatically reducing their exit rate. Proteasome sequestration is persistent, reflecting an association with the actin-based cytoskeleton. Together, our data indicate that synaptic activity can promote the recruitment and sequestration of proteasomes to locally remodel the protein composition of synapses.
authors.forename: Baris
authors.initials: B
authors.lastname: Bingol
authors.forename: Erin M
authors.initials: EM
authors.lastname: Schuman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D038761:Photobleaching; D011189:Potassium Chloride / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D016194:Receptors, N-Methyl-D-Aspartate; D011189:Potassium Chloride; D046988:Proteasome Endopeptidase Complex