Nature Neuroscience6, 231 - 242 (2003)
Published online: 10 February 2003; | doi:10.1038/nn1013
There is a Corrigendum (March 2006) associated with this Article.
Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system
Michael D. Ehlers
Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA. ehlers@neuro.duke.edu
Experience-dependent remodeling of the postsynaptic density (PSD) is critical for synapse formation and plasticity in the mammalian brain. Here, in cultured rat hippocampal neurons, I found long-lasting, global changes in the molecular composition of the PSD dictated by synaptic activity. These changes were bidirectional, reversible, modular, and involved multiple classes of PSD proteins. Moreover, activity-dependent remodeling was accompanied by altered protein turnover, occurred with corresponding increases or decreases in ubiquitin conjugation of synaptic proteins and required proteasome-mediated degradation. These modifications, in turn, reciprocally altered synaptic signaling to the downstream effectors CREB (cyclic AMP response element binding protein) and ERK-MAPK (extracellular signal regulated kinase−MAP kinase). These results indicate that activity regulates postsynaptic composition and signaling through the ubiquitin-proteasome system, providing a mechanistic link between synaptic activity, protein turnover and the functional reorganization of synapses.
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