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Nat Neurosci. 2003 Mar;6(3):231-42.

Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system.

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Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA.

Erratum in

  • Nat Neurosci. 2006 Mar;9(3):453.


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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