Autophosphorylated CaMKIIα Acts as a Scaffold to Recruit Proteasomes to Dendritic Spines

The molecular mechanisms regulating the ubiquitin proteasome system (UPS) at synapses are poorly understood. We report that CaMKII alpha-an abundant postsynaptic protein kinase-mediates the activity-dependent recruitment of proteasomes to dendritic spines in hippocampal neurons. CaMKII alpha is biochemically associated with proteasomes in the brain. CaMKII alpha translocation to synapses is required for activity-induced proteasome accumulation in spines, and is sufficient to redistribute proteasomes to postsynaptic sites. CaMKII alpha autophosphorylation enhances its binding to proteasomes and promotes proteasome recruitment to spines. In addition to this structural role, CaMKII alpha stimulates proteasome activity by phosphorylating proteasome subunit Rpt6 on Serine 120. However, CaMKII alpha translocation, but not its kinase activity, is required for activity-dependent degradation of polyubiquitinated proteins in spines. Our findings reveal a scaffolding role of postsynaptic CaMKII alpha in activity-dependent proteasome redistribution, which is commensurate with the great abundance of CaMKII alpha in synapses.