NDLI: Regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase II.

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Regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase II.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Djakovic, Stevan N. Schwarz, Lindsay A. Demartino, George N. Barylko, Barbara Patrick, Gentry N.
Description	Author Affiliation: Djakovic SN ( Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0347, USA.)
Abstract	Protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. It is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. By utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. We find that the blockade of action potentials (APs) with tetrodotoxin inhibited the activity of the proteasome, whereas the up-regulation of APs with bicuculline dramatically increased the activity of the proteasome. In addition, the regulation of the proteasome is dependent upon external calcium entry in part through N-methyl-D-aspartate receptors and L-type voltage-gated calcium channels and requires the activity of calcium/calmodulin-dependent protein kinase II (CaMKII). Using in vitro and in vivo assays we find that CaMKII stimulates proteasome activity and directly phosphorylates Rpt6, a subunit of the 19 S (PA700) subcomplex of the 26 S proteasome. Our data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	39
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-09-25
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcium-Calmodulin-Dependent Protein Kinase Type 2 Metabolism Neurons Proteasome Endopeptidase Complex Action Potentials Drug Effects Animals Calcium Pharmacology Genetics Cell Line Cells, Cultured Dendrites Physiology Green Fluorescent Proteins Hippocampus Cytology Immunoprecipitation Microscopy, Confocal Mutation Phosphorylation Sodium Channel Blockers Tetrodotoxin Transfection Ubiquitin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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